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Abstract To assess the agreement and repeatability of scotopic pupil size measurement using 2WIN-S (Adaptica, Padova, Italy) portable refractor in Chinese adults. This prospective non-randomized open-label controlled study assessed the scotopic pupil size of 100 right eyes using OPD-Scan III (Optical path difference) (Nidek Technologies, Gamagori, Japan) and 2WIN-S. OPD-Scan III and 2WIN-S measure pupil size using infrared light and detector, while 2WIN-S measures bilateral eyes simultaneously, OPD-Scan III measures unilateral eyes individually. Participants were first measured once using OPD-Scan III and two consecutive measurements were performed using 2WIN-S after 15 min of rest interval. The primary outcome was to evaluate the agreement between 2WIN-S and OPD-Scan III, and the secondary outcome was to evaluate the repeatability of 2WIN-S. Scotopic pupil size of 100 right eyes of 100 adults (28 male and 72 female) aged 18–53 years (mean 36 ± 12 years) was assessed using OPD-Scan III and 2WIN-S, respectively. The mean scotopic pupil size of OPD-Scan III and 2WIN-S was recorded to be 6.24 ± 0.88 mm and 6.27 ± 0.81 mm, respectively. For the mean scotopic pupil size of OPD-Scan III and 2WIN-S the difference was − 0.03 mm (95%CI − 0.10 to 0.04 mm), p = 0.445, the 95% limits of agreement (LOA) was − 0.71 to 0.66 mm. ICC between the two devices was 0.92 (95% CI 0.88–0.94) (ICC > 0.9 indicates excellent consistency). Coefficients of repeatability (CoR) of 2WIN-S was 0.37, which has a high repeatability. For the mean scotopic pupil size of 2WIN-S of the repeated measurements, the difference was -0.04 mm (95%CI − 0.08 to 0.01 mm), p = 0.019, the 95% limits of agreement (LOA) was − 0.41 to 0.32 mm, with a narrow LOA. However, the majority of the variations were less than ± 0.50 mm (98% of scotopic pupil size measurements were below this threshold), within the clinically acceptable range (± 0.50 mm). Our study showed excellent agreement between 2WIN-S and OPD-Scan III (ICC > 0.9) and a good repeatability of 2WIN-S (CoR = 0.37). This study suggests a novel technique for measuring pupillary responses in low light conditions, which can be considered an alternative to OPD-Scan III in clinical settings.

Abstract Checkpoint kinase 1 (CHK1) is critical for cell survival under replication stress (RS). CHK1 inhibitors (CHK1i’s) in combination with chemotherapy have shown promising results in preclinical studies but have displayed minimal efficacy with substantial toxicity in clinical trials. To explore combinatorial strategies that can overcome these limitations, we perform an unbiased high-throughput screen in a non-small cell lung cancer (NSCLC) cell line and identify thioredoxin1 (Trx1), a major component of the mammalian antioxidant-system, as a determinant of CHK1i sensitivity. We establish a role for redox recycling of RRM1, the larger subunit of ribonucleotide reductase (RNR), and a depletion of the deoxynucleotide pool in this Trx1-mediated CHK1i sensitivity. Further, the TrxR inhibitor auranofin, an approved anti-rheumatoid arthritis drug, shows a synergistic interaction with CHK1i via interruption of the deoxynucleotide pool. Together, we show a pharmacological combination to treat NSCLC that relies on a redox regulatory link between the Trx system and mammalian RNR activity.

Root-associated microorganisms, which can be recruited specially by plants to cope with environmental stress under extreme conditions, are one of the major mediators of nutrient exchange between plants and the environment. To obtain more crop-beneficial microbes, rhizosphere bacteria of Désirée potatoes cultivated in poor and alkaline soil have been studied. The screening of 83 strains with incomplete identical 16S rDNA sequences showed that 47 strains produced indole acetic acid (IAA), with contents ranging from 0.2 to 42 mg/L, and seven strains were phosphorus-solubilizing, among which six strains significantly increased the growth rate of potato plants. Thirty-seven strains produced siderophore and four strains were zinc-solubilizing, among which three strains significantly alleviated the chlorosis of potato plants. In all of the isolates, the species Variovorax soli (ST98) and Cellulomonas biazotea (ST118) were first found to possess an IAA-secreting ability; the species Leifsonia aquatica (ST172) and Leifsonia naganoensis (ST177) and the genus Sutcliffiella (ST11) were first discovered to be capable of phosphorus solubilization; the species Chryseobacterium daecheongense (ST32) was the first reported to be capable of zinc solubilization; and the species V. soli (ST98), C. biazotea (ST118) and L. naganoensis (ST177) were first found to be capable of plant growth promotion. The discovery of multiple functional bacteria enriched the resources of plant growth-promoting bacteria and provided a foundation for biofertilizer production to improve soil conditions and crop production.

The aim of this study was to explore the immunomodulatory effect of Polygonatum sibiricum saponin (PS) in a cyclophosphamide-induced (Cy) immunosuppression mice model. Oral administration of PS by gavage effectively alleviated weight loss caused by Cy and increased the index of immune organs. PS promoted the proliferation of splenic lymphocytes and T cell subsets (CD3+, CD355+, CD4+/CD8+) and relieved the xylene-induced inflammatory response and Cy-induced increase of serum hemolysin. Moreover, PS increased serum levels of lactate dehydrogenase and acid phosphatase. PS elevated serum level of cytokines and immunoglobulins (TNF-α, IFN-γ, IL-4, IL-6, IL-β, SIgA, and IgG) and the expression of mRNA of IL-10, TNF-α, and IL-6 in the spleen. Increased mRNA expression of tight junction protein (ZO-1, Mucin2, Occludin) expression and protein expression of IL-6/MyD88/TLR4 in the small intestine showed that PS exhibited a restorative effect on intestinal mucosal injury caused by cyclophosphamide. Oral PS prevented Cy-induced decline in leukocytes, red blood cells, lymphocytes, hemoglobin concentrations, and neutrophils, providing evidence for alleviating hematopoietic disorders. In addition, PS increased SOD and NO levels, reduced MDA levels, and improved oxidative damage in the liver. These findings demonstrate that PS has the potential to be developed as a supplemental agent for alleviating immunosuppression caused by chemotherapeutic agents.

To prevent alcoholic liver disease, the addition of bioactive substances to the alcoholic drink Baijiu has been considered a feasible option. In the present study, the hepatoprotective effects of a sea cucumber sulfated polysaccharide (SCSP) isolated from Stichopus japonicu were investigated. Moreover, in order to enhance its solubility in an alcohol solution, it was depolymerized using a photocatalytic reaction, and the photocatalytic degradation products (dSCSPs) with an average molecular weight of less than 2 kDa were studied and compared with SCSP. They were characterized by a series of chemical and spectroscopy methods and the oligosaccharide fragments in the dSCSP were further identified by HPLC-MSn analysis. Then, the in vivo experiment showed that the addition of SCSP or dSCSP to Baijiu could alleviate alcoholic liver injury in mice. Further analysis also revealed their protective effect in reducing oxidative stress damage and their regulation of the metabolism of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in the liver. Of note, dSCSP was more effective at reducing the level of malondialdehyde in the liver. These findings indicate that the addition of sea cucumber polysaccharide or its low-molecular-weight derivative in Baijiu has the potential to alleviate alcoholic liver injury.

Due to its significant physiological effects, a sulfated polysaccharide has been considered an important nutrient of sea cucumber, but its metabolism in vivo is still unclear. The present study investigated the metabolism of a sea cucumber sulfated polysaccharide (SCSP) in rats and its influence on the metabolite profiles. The quantification by HPLC-MS/MS revealed that the blood level of SCSP achieved a maximum of 54.0 ± 4.8 μg/mL at 2 h after gavage, almost no SCSP was excreted through urine, and 55.4 ± 29.8% of SCSP was eliminated through feces within 24 h. These results prove the utilization of SCSP by gut microbiota, and a further microbiota sequencing analysis indicated that the SCSP utilization in the gut was positively correlated with Muribaculaceae and Clostridia_UCG-014. In addition, the non-targeted metabolomic analysis demonstrated the significant effects of SCSP administration on the metabolite profiles of blood, urine, and feces. It is worth noting that the SCSP supplement decreased palmitic acid, stearic acid, and oleic acid in blood and urine while increasing stearic acid, linoleic acid, and γ-linolenic acid in feces, suggesting the inhibition of fat absorption and the enhancement of fat excretion by SCSP, respectively. The present study shed light on the metabolism in vivo and the influence on the fat metabolism of SCSP.

Ferroptosis, a new form of non-apoptotic, regulated cell death characterized by iron dependency and lipid peroxidation, is involved in many pathological conditions such as neurodegenerative diseases, heart ischemia/reperfusion injury, acute renal failure, and cancer. While metabolic dysfunctions can lead to excessive lipid peroxidation culminating in ferroptotic cell death, glutathione peroxidase 4 (GPX4) resides in the center of a network that functions to prevent lipid hydroperoxides from accumulation, thereby suppressing ferroptosis. Indeed, RSL3 and other small-molecule GPX4 inhibitors can induce ferroptosis in not only cultured cancer cells but also tumor xenografts implanted in mice. Similarly, erastin and other system Xc− inhibitors can deplete intracellular glutathione required for GPX4 function, leading to lipid peroxidation and ferroptosis. As therapy-resistant cancer cells are sensitive to GPX4-targeted therapeutic regimens, the agents capable of inducing ferroptosis hold great promises to improve current cancer therapy. This review will outline the molecular basis of ferroptosis, but focus on the strategies and the agents developed in recent years for therapeutic induction of ferroptosis. The potentials of these ferroptosis-inducing agents, which include system Xc− inhibitors, GPX4 inhibitors, and iron-based nanoparticles, in cancer therapy will be subsequently discussed.

Abstract Purpose A real-time automatic cataract-grading algorithm based on cataract video is proposed. Materials and methods In this retrospective study, we set the video of the eye lens section as the research target. A method is proposed to use YOLOv3 to assist in positioning, to automatically identify the position of the lens and classify the cataract after color space conversion. The data set is a cataract video file of 38 people's 76 eyes collected by a slit lamp. Data were collected using five random manner, the method aims to reduce the influence on the collection algorithm accuracy. The video length is within 10 s, and the classified picture data are extracted from the video file. A total of 1520 images are extracted from the image data set, and the data set is divided into training set, validation set and test set according to the ratio of 7:2:1. Results We verified it on the 76-segment clinical data test set and achieved the accuracy of 0.9400, with the AUC of 0.9880, and the F1 of 0.9388. In addition, because of the color space recognition method, the detection per frame can be completed within 29 microseconds and thus the detection efficiency has been improved significantly. Conclusion With the efficiency and effectiveness of this algorithm, the lens scan video is used as the research object, which improves the accuracy of the screening. It is closer to the actual cataract diagnosis and treatment process, and can effectively improve the cataract inspection ability of non-ophthalmologists. For cataract screening in poor areas, the accessibility of ophthalmology medical care is also increased.

Abstract Metabolic reprogramming is an integral part of the growth-promoting program driven by the MYC family of oncogenes. However, this reprogramming also imposes metabolic dependencies that could be exploited therapeutically. Here we report that the pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase (DHODH) is an attractive therapeutic target for MYCN-amplified neuroblastoma, a childhood cancer with poor prognosis. Gene expression profiling and metabolomic analysis reveal that MYCN promotes pyrimidine nucleotide production by transcriptional upregulation of DHODH and other enzymes of the pyrimidine-synthesis pathway. Genetic and pharmacological inhibition of DHODH suppresses the proliferation and tumorigenicity of MYCN-amplified neuroblastoma cell lines. Furthermore, we obtain evidence suggesting that serum uridine is a key factor in determining the efficacy of therapeutic agents that target DHODH. In the presence of physiological concentrations of uridine, neuroblastoma cell lines are highly resistant to DHODH inhibition. This uridine-dependent resistance to DHODH inhibitors can be abrogated by dipyridamole, an FDA-approved drug that blocks nucleoside transport. Importantly, dipyridamole synergizes with DHODH inhibition to suppress neuroblastoma growth in animal models. These findings suggest that a combination of targeting DHODH and nucleoside transport is a promising strategy to overcome intrinsic resistance to DHODH-based cancer therapeutics.

Gliomas are the most common primary intracranial neoplasms among all brain malignancies, and the microtubule affinity regulating kinases (MARKs) have become potential drug targets for glioma. Here, we report a novel dual small-molecule inhibitor of MARK3 and MARK4, designated as PCC0208017. In vitro, PCC0208017 strongly inhibited kinase activity against MARK3 and MARK4, and strongly reduced proliferation in three glioma cell lines. This compound attenuated glioma cell migration, glioma cell invasion, and angiogenesis. Molecular mechanism studies revealed that PCC0208017 decreased the phosphorylation of Tau, disrupted microtubule dynamics, and induced a G2/M phase cell cycle arrest. In an in vivo glioma model, PCC0208017 showed robust anti-tumor activity, blood–brain barrier permeability, and a good oral pharmacokinetic profile. Molecular docking studies showed that PCC0208017 exhibited high binding affinity to MARK3 and MARK4. Taken together, our study describes for the first time that PCC0208017, a novel MARK3/MARK4 inhibitor, might be a promising lead compound for treatment of glioma. Key words: Glioma, PCC0208017, MARK3, MARK4, Molecular docking

Dysfunction of p53 is observed in many malignant tumors, which is related to cancer susceptibility. In cervical cancer, p53 is primarily degradated through the complex of high-risk human papillomaviruses (HPV) oncoprotein E6 and E6-associated protein (E6AP) ubiquitin ligase. What is less clear is the mechanism and role of murine double minute X (MDMX) in cervical carcinogenesis due to the inactive status of murine double minute 2 (MDM2). In the current study, XI-011 (NSC146109), a small-molecule inhibitor of MDMX, showed robust anti-proliferation activity against several cervical cancer cell lines. XI-011 promoted apoptosis of cervical cancer cells via stabilizing p53 and activating its transcription activity. Moreover, XI-011 inhibited the growth of xenograft tumor in HeLa tumor-bearing mice, as well as enhanced the cytotoxic activity of cisplatin both in vitro and in vivo. Interestingly, MDMX co-localized with E6AP and seems to be a novel binding partner of E6AP to promote p53 ubiquitination. In conclusion, this work revealed a novel mechanism of ubiquitin-dependent p53 degredation via MDMX-E6AP axis in cervical carcinogenesis, and offered the first evidence that MDMX could be a viable drug target for the treatment of cervical cancer.

Summary: The serine synthesis pathway (SSP) involving metabolic enzymes phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1), and phosphoserine phosphatase (PSPH) drives intracellular serine biosynthesis and is indispensable for cancer cells to grow in serine-limiting environments. However, how SSP is regulated is not well understood. Here, we report that activating transcription factor 3 (ATF3) is crucial for transcriptional activation of SSP upon serine deprivation. ATF3 is rapidly induced by serine deprivation via a mechanism dependent on ATF4, which in turn binds to ATF4 and increases the stability of this master regulator of SSP. ATF3 also binds to the enhancers/promoters of PHGDH, PSAT1, and PSPH and recruits p300 to promote expression of these SSP genes. As a result, loss of ATF3 expression impairs serine biosynthesis and the growth of cancer cells in the serine-deprived medium or in mice fed with a serine/glycine-free diet. Interestingly, ATF3 expression positively correlates with PHGDH expression in a subset of TCGA cancer samples.

The present study aimed to clarify the potential mechanism of fucoidans found in Ascophyllum nodosum on anti-inflammation and to further explore the relationship between their structures and anti-inflammation. Two novel fucoidans named ANP-6 and ANP-7 and found in A. nodosum, were separated and purified and their structures were elucidated by HPGPC, HPLC, GC-MS, FT-IR, NMR, and by the Congo red test. They both possessed a backbone constructed of →2)-α-L-Fucp4S-(1→, →3)-α-L-Fucp2S4S-(1→, →6)-β-D-Galp-(1→, and →3,6)-β-D-Galp4S-(1→ with branches of →2)-α-L-Fucp4S-(1→ and →3)-β-D-Galp-(1→. Moreover, ANP-6 and ANP-7 could prevent the inflammation of the LPS-stimulated macrophages by suppressing the NO production and by regulating the expressions of iNOS, COX-2, TNF-α, IL-1β, IL-6, and IL-10. Their inhibitory effects on the TLR-2 and TLR-4 levels suggest that they inhibit the inflammation process via the blocking of the TLR/NF-κB signal transduction. In addition, ANP-6, with a molecular weight (63.2 kDa), exhibited stronger anti-inflammatory capabilities than ANP-7 (124.5 kDa), thereby indicating that the molecular weight has an influence on the anti-inflammatory effects of fucoidans.

Purpose. As part of plans to provide help to people in remote and poor areas who have no medical resources, a portable slit-lamp based on a smartphone was proposed. This would help in early screening of cataract diseases. Methods. This means a microlens is designed that would work with a phone’s camera. The phone’s photo taking function is used in capturing the image of the eyes lens to replace the observation system of the desktop slit-lamp. A simplified slit light band was designed. In order for the light source part to meet the portable requirements of the slit-lamp, the adjustable and diffused light functions of the ligaments were removed in this design. Furthermore, the images collected by the smartphone are uploaded to the deep learning cataract screening system, which can achieve real-time and effective screening of cataract. Results. Unlike the desktop slit-lamp, which needs skilled personnel to operate, this device can be easily operated by less-skilled or inexperienced doctors. This eliminates the concerns of inaccurate diagnosis based on the use of unskilled professionals. Due to the portability, ease of use, and simplicity in obtaining crystal images of this device, it serves as a promising platform for nonhospital screening and telemedicine. Conclusions. In this paper, we invented a small portable device for screening cataract. This device is to make screening and diagnosis of cataract in remote areas very fast and effective. It will also solve the problem of inadequate specialized doctors and equipment in those areas as well. Translational Relevance. Smartphones can be used with portable slit-lamps to capture the images of the lens.

Imaging tracking of the migration of cell-based drug delivery systems are needed for expanding their clinical application for glioma. Here they report inflammation activatable engineered neutrophils containing doxorubicin-loaded magnetic mesoporous silica nanoparticles to image and actively target brain tumors after resection.

Tubulin has been shown to be an effective target for the development of cytotoxic agents against prostate cancer. Previously, we reported that Lx2-32c is an anti-tubulin agent with high binding affinity to tubulin. In this study, we investigated the potential of Lx2-32c to act as an effective cytotoxic agent in the treatment of prostate cancer. MTT assays showed that Lx2-32c was cytotoxic to all tested prostate cancer cell lines. The Lx2-32c-treated cells typically exhibited a rounded morphology associated with the onset of apoptosis, as evidenced by immunocytochemical staining. Human prostate cancer cell lines treated with Lx2-32c arrest in the G2/M phase of the cell cycle and the treatment is associated with an increased ratio of cells in the sub-G0/G1 phase as determined by flow cytometry. Furthermore, expression of the cleaved form of poly (ADP-ribose) polymerase in prostate cancer cell lines treated with Lx2-32c was shown by Western blotting assay. Xenograft implants of LNCaP and PC3-derived tumors in nude mice showed that Lx2-32c treatment significant inhibited tumor growth with effects equivalent to those of docetaxel. These findings demonstrate the potential of Lx2-32c as a candidate antitumor agent for the treatment of prostate cancer.

High-risk neuroblastoma remains one of the deadliest childhood cancers. Identification of metabolic pathways that drive or maintain high-risk neuroblastoma may open new avenues of therapeutic interventions. Here, we report the isolation and propagation of neuroblastoma sphere-forming cells with self-renewal and differentiation potential from tumors of the TH-MYCN mouse, an animal model of high-risk neuroblastoma with MYCN amplification. Transcriptional profiling reveals that mouse neuroblastoma sphere-forming cells acquire a metabolic program characterized by transcriptional activation of the cholesterol and serine-glycine synthesis pathways, primarily as a result of increased expression of sterol regulatory element binding factors and Atf4, respectively. This metabolic reprogramming is recapitulated in high-risk human neuroblastomas and is prognostic for poor clinical outcome. Genetic and pharmacological inhibition of the metabolic program markedly decreases the growth and tumorigenicity of both mouse neuroblastoma sphere-forming cells and human neuroblastoma cell lines. These findings suggest a therapeutic strategy for targeting the metabolic program of high-risk neuroblastoma.

The histone lysine demethylase KDM4C is often overexpressed in cancers primarily through gene amplification. The molecular mechanisms of KDM4C action in tumorigenesis are not well defined. Here, we report that KDM4C transcriptionally activates amino acid biosynthesis and transport, leading to a significant increase in intracellular amino acid levels. Examination of the serine-glycine synthesis pathway reveals that KDM4C epigenetically activates the pathway genes under steady-state and serine deprivation conditions by removing the repressive histone modification H3 lysine 9 (H3K9) trimethylation. This action of KDM4C requires ATF4, a transcriptional master regulator of amino acid metabolism and stress responses. KDM4C activates ATF4 transcription and interacts with ATF4 to target serine pathway genes for transcriptional activation. We further present evidence for KDM4C in transcriptional coordination of amino acid metabolism and cell proliferation. These findings suggest a molecular mechanism linking KDM4C-mediated H3K9 demethylation and ATF4-mediated transactivation in reprogramming amino acid metabolism for cancer cell proliferation.

The aim of this study was to determine whether thymoquinone, the principal active ingredient in the volatile oil of Nigella sativa seeds, could suppress certain virulence traits of Cronobacter sakazakii ATCC 29544 which contribute to infection. Sub-inhibitory concentrations of thymoquinone significantly decreased motility, quorum sensing, and endotoxin production of C. sakazakii ATCC 29544 and biofilm formation of C. sakazakii 7-17. Thymoquinone substantially reduced the adhesion and invasion of C. sakazakii ATCC 29544 to HT-29 cells and decreased the number of intracellular bacterial cells within the RAW 264.7 macrophage cells. Thymoquinone also repressed the transcription of sixteen genes involved in the virulence. These findings suggest that thymoquinone could attenuated virulence-related traits of C. sakazakii ATCC 29544, and its effects on other C. sakazakii strains and in vivo C. sakazakii infection need further investigation.

The tumor suppressor p53 is often inactivated in breast cancer cells because the overexpression of its repressors (e.g., MDM2 and MDMX). Restoration of p53 activity by small molecules through counteracting p53 repressors can lead to in vivo tumor regression and is therefore considered a promising strategy for treatments of cancer. Recent efforts in high-throughput drug screening and rational drug design have identified several structurally diverse small-molecule p53 activators, including a pseudourea derivative XI-011 (NSC146109). This small molecule strongly activates p53 while selectively inhibiting growth of transformed cells without inducing genotoxicity, indicating its potential as a drug lead for p53-targeted therapy. However, the mechanism(s) by which XI-011 activates p53 and the effects of XI-011 on growth of breast cancer cells are currently unknown. Here, we report that XI-011 promoted breast cancer cells to undergo apoptosis through activating p53 and inducing expression of proapoptotic genes. Importantly, we found that activation of p53 by this small molecule was achieved through a novel mechanism, that is, inhibition of MDMX expression. XI-011 repressed the MDMX promoter, resulting in down-regulation of MDMX messenger RNA level in MCF-7 cells. In line with these results, XI-011 decreased the viability of breast cancer cells expressing low levels of MDMX in a less-efficient manner. Interestingly, XI-011 acted additively with the MDM2 antagonist Nutlin-3a to inhibit growth of breast cancer cells. We conclude that XI-011 belongs to a novel class of small-molecule p53 activators that target MDMX and could be of value in treating breast cancer.

Li Li1, XinYu Zhang1, ChunHong Yan1, QingXiang Liang21Biomedical Engineering Lab, Faculty of Information Engineering, ShenZhen University, ShenZhen, China; 2Bao An People’s Hospital, ShenZhen, ChinaObjective: Extensive marketing of devices for self-measurement of blood pressure has created a need for purchasers to be able to satisfy themselves that such devices have been evaluated according to agreed criteria. The Oregon Scientific BPU 330 blood pressure monitor is an electronic device for upper arm measurement. This study assessed the accuracy of the Oregon Scientific BPU 330 blood pressure monitor according to the International Protocol by the Working Group on Blood Pressure Monitoring of the European Society of Hypertension for validation of blood pressure measuring devices.Method: 52 participants over 30 years of age were studied in the validation. Nine blood pressure measurements were taken alternately with a mercury sphygmomanometer by two observers, and by the supervisor, using the BPU 330 device. A total of 33 participants were selected for the analysis. The validation was divided into two phases. Phase 1 included 15 participants. If the device passed phase 1, 18 more participants were included. The 99 pairs of measurements were compared according to the International Protocol. The device was given a pass/fail recommendation based on its accuracy compared with the mercury standard (within 5, 10, and 15 mmHg), as well as the number met in the ranges specified by the International Protocol.Results: The mean and standard deviation of the difference between the mean of the observers and the BPU 330 device were 1.7 ± 4.7 mmHg and 2.8 ± 3.9 mmHg for systolic blood pressure (SBP) and diastolic blood pressure (DBP), respectively. In phase 1, the device passed with a total of 33, 43, and 44 SBP readings; 38, 44, and 45 DBP readings were within 5, 10, and 15 mmHg, respectively. In phase 2.1, 81, 95, and 96 for SBP, and 83, 95, and 98 for DBP readings fell within the zones of 5, 10, and 15 mmHg, respectively. In phase 2.2, the last phase, 28 participants fell within the zone of two of the three comparisons, lying within 5 mmHg for SBP and 29 participants for DBP. No participants fell within the zone of all three of their comparisons over 5 mmHg apart for both SBP and DBP.Conclusion: The BPU 330 can be recommended for self-monitoring of blood pressure in the adult population, according to the International Protocol.Keywords: blood pressure, self-monitoring, hypertension, International Protocol

The dineolignan manassantin A from Saururaceae was recently identified as a hypoxia-inducible factor 1 (HIF-1) inhibitor, but its in-vivo anti-tumor effect has not been explored. We synthesized a series of manassantin A derivatives, and found that replacing the central tetrahydrofuran moiety with a cyclopentane ring yielded a compound (LXY6006) with increased HIF-1-inhibitory activity yet decreased stereochemically complexity amenable to a simplified synthesis scheme. LXY6006 inhibited HIF-1α nuclear accumulation induced by hypoxia, and inhibited cancer cell growth as a consequence of G2/M arrest. Oral administration of LXY6006 significantly inhibited growth of breast, lung, and pancreatic tumors implanted in nude mice. These results indicate that LXY6006 represents a novel class of agents targeting a broad range of human cancers.

Abstract Background Olfactory function is closely related to mood and the endocrine system. However, the role of olfactory function in bipolar disorder combined with metabolic syndrome remains unclear. The purpose of this study was to explore the associations among olfactory function, tumor necrosis factor alpha (TNF-α), and metabolic syndrome and its components in patients with bipolar disorder. Methods Ninety-six bipolar disorder patients were divided into two groups with and without metabolic syndrome. We also included 46 healthy controls. Olfactory function was assessed using the Sniffin’ Sticks test. Blood samples were collected to measure metabolic indicators and serum TNF-α levels. Results Significant differences in olfactory function were found among the three groups. Compared with the healthy controls, the bipolar disorder without metabolic syndrome group showed poorer olfactory identification ability (P