Oral treatment with plecanatide or dolcanatide attenuates visceral hypersensitivity via activation of guanylate cyclase-C in rat models

AIM To investigate the effects of plecanatide and dolcanatide on maintenance of paracellular permeability, integrity of tight junctions and on suppression of visceral hypersensitivity. METHODS Transport of fluorescein isothiocyanate(FITC)-dextran was measured to assess permeability across cell monolayers and rat colon tissues. Effects of plecanatide and dolcanatide on the integrity of tight junctions in Caco-2 and T84 monolayers and on the expression and localization of occludin and zonula occludens-1(ZO-1) were examined by immunofluorescence microscopy. Anti-nociceptive activity of these agonists was evaluated in trinitrobenzene sulfonic acid(TNBS)-induced inflammatory as well as in non-inflammatory partial restraint stress(PRS) rat models. Statistical significance between the treatment groups in the permeability studies were evaluated using unpaired t-tests.RESULTS Treatment of T84 and Caco-2 monolayers with lipopolysaccharide(LPS) rapidly increased permeability, which was effectively suppressed when monolayers were also treated with plecanatide or dolcanatide. Similarly, when T84 and Caco-2 monolayers were treated with LPS, cell surface localization of tight junction proteins occludin and ZO-1 was severely disrupted. When cell monolayers were treated with LPS in the presence of plecanatide or dolcanatide, occludin and ZO-1 were localized at the cell surface of adjoining cells, similar to that observed for vehicle treated cells. Treatment of cell monolayers with plecanatide or dolcanatide without LPS did not alter permeability, integrity of tight junctions and cell surface localization of either of the tight junction proteins. In rat visceral hypersensitivity models, both agonists suppressed the TNBS-induced increase in abdominal contractions in response to colorectal distension without affecting the colonic wall elasticity, and both agonists also reduced colonic hypersensitivity in the PRS model. CONCLUSION Our results suggest that activation of GC-C signaling might be involved in maintenance of barrier function, possibly through regulating normal localization of tight junction proteins. Consistent with these findings, plecanatide and dolcanatide showed potent antinociceptive activity in rat visceral hypersensitivity models. These results imply that activation of GC-C signaling may be an attractive therapeutic approach to treat functional constipation disorders and inflammatory gastrointestinal conditions.

A new cytotoxic caged polyprenylated xanthone from the resin of Garcinia hanburyi

A new caged polyprenylated xanthone, gambogic aldehyde （1）, was isolated from the resin of Garcinia hanburyi. Its structure was elucidated on the basis of spectral data including 1D and 2D NMR data. In addition, the antiproliferative ability of compound 1 was determined in mouse leukemia P388 and P388/ADR cells.

Suboxone Prescribing Availability in Orange County, NY

Background: The opioid epidemic is a major threat to public health in the United States of America. Orange County, New York has been chosen for this study of Suboxone, a prescription medicine that is used to treat addiction to opioid analgesics. This drug is underutilized throughout Orange County because of several impediments, including insurance coverage, social stigmas, and a non-compliant patient population. Objective: The objective is to analyze the accessibility and utilization of Suboxone to treat opioid dependence in Orange County, New York. Method: Two survey instruments have been created for this research project, one for Suboxone providers and one for non-Suboxone providers. Each is 10 questions long, and includes multiple choice and open-response questions. Participants were contacted by means of email and telephone. Results: The results displayed that many Suboxone providers prefer not treating this patient population for the following reasons: insurance coverage problems, lack of time to see these demanding patients, and a non-compliant patient population. Almost all of the doctors surveyed believed that there is a social stigma among physicians to prescribe as well as among patients to use Suboxone. The non-Suboxone providers did not want to prescribe Suboxone because of a non-compliant patient population, and not having enough time in their practice. Almost all of the non-Suboxone providers prescribed other opiates. For most of the doctors, having more ancillary staff (psychologists, physical therapists, mid level providers) would motivate them to prescribe Suboxone. Discussion and Conclusion: Recommendations made by the local physicians for treating the current opioid epidemic include the following: more police enforcement of street drug dealers, patient education of narcotic misuse, physician education of both the opioid epidemic and patient treatment, and expanding access to rehabilitation and care for these patients.

Improved Pregnancy Outcomes in a Prospective Study of Pregnant Women Enrolling in an Antenatal Clinic in Western Kenya

In areas of sub-Saharan Africa where malaria is endemic, pregnant women are at a greater risk of malaria than non-pregnant women leading to significant adverse consequences including anemia, intrauterine growth retardation, low birth weight (LBW), and pre-term delivery. The Kenya Ministry of Health adopted Intermittent Preventive Treatment (IPT) and use of insecticide-treated nets (ITN) as a National strategy for malaria prevention in pregnancy. In this report, we evaluated the prevalence of malaria, the anthropometric measures of birth outcomes and the reasons for loss to follow up among pregnant women participating in an ongoing cohort study in Western Kenya. A total of 175 HIV-negative pregnant women enrolled at antenatal clinic of Chulaimbo sub-District hospital were longitudinally evaluated in a monthly follow-up visits through antenatal visits (up to 4 per mother) and delivery. Thirty three percent and 15% of the pregnant women were malaria positive by real-time quantitative (Q)-PCR and microscopy respectively at enrolment, while 54% and 23% of the pregnant women had malaria by Q-PCR and microscopy respectively at any time during follow-up. Of the enrolled study participants, 65% delivered at Chulaimbo hospital. Overall, 39% (69) of the pregnant women were lost to follow-up. The major reasons for loss to follow up were relocation from the study area (26%) and delivery at alternative health facilities (25%). The mean birth weight of the newborn infants was 3202 g (range, 2000 g - 4000 g). Only 5.3% of the infants weighed less than 2500 g (low birth weight). The mean head circumference was 34 cm (range, 30 cm - 39 cm) with mean Apgar score (at 10 minutes) ± S.D. of 9.8 ± 0.97. In conclusion, we observed decreased adverse pregnancy outcomes among our study population. We recommend a larger study of all pregnant women attending the Chulaimbo hospital so as to assess whether effectiveness of malaria and anemia control programs lead to improved birth outcomes.

Stony Brook’s High-Pressure Laboratory Collaborations with French Scientists

For more than a half century, my colleagues and I in the Stony Brook High Pressure Laboratory have profited from collaborations with French scientists in their laboratories in Orsay, Paris, Toulouse, Lille, Lyon, Strasbourg and Rennes. These interactions have included postdoctoral appointments of French colleagues in our laboratory as well as two année sabbatique by me;in 1983-84, in the Laboratoire de Géophysique et Géodynamique Interne at the Université Paris XI in Orsay and in 2020-2003 in the Laboratoire des Méchanismes et Transfert en Géologie at the Université Paul Sabatier in Toulouse. The objective of this report is to relate this history and to illustrate the scientific advances which resulted from these collaborations.

Stony Brook’s Collaborations with Czech Scientists

For the past half-century, I have been fortunate in maintaining collaborations with Czech scientists in the Czech Republic [formerly Czechoslovakia] from the Geofyzikální ústav-GFU [Institute of Geophysics] of the ?eskoslovenská Akademie Věd-?SAV [Czechoslovak Academy of Sciences]. These collaborations have included exchange visits by me to Prague [Praha] and convening international workshops in 1976, 1986 and 1996 in castles used by the ?SAV as well as visits by Czech colleagues to Stony Brook University. The objective of this report is to relate this history. This paper is dedicated to the memory of Vladislav Babu?ka.

Capsule endoscopy in Crohn's disease: Are we seeing any better?

Crohn’s disease (CD) is a complex, immune-mediated disorder that often requires a multi-modality approach for optimal diagnosis and management. While traditional methods include ileocolonoscopy and radiologic modalities, increasingly, capsule endoscopy (CE) has been incorporated into the algorithm for both the diagnosis and monitoring of CD. Multiple studies have examined the utility of this emerging technology in the management of CD, and have compared it to other available modalities. CE offers a noninvasive approach to evaluate areas of the small bowel that are difficult to reach with traditional endoscopy. Furthermore, CE maybe favored in specific sub segments of patients with inflammatory bowel disease (IBD), such as those with IBD unclassified (IBD-U), pediatric patients and patients with CD who have previously undergone surgery.

Molecular Phylogeny of the Genus Gloydius(Serpentes: Crotalinae)

Based on two mitochondrial genes (cyt b, ND4) and one nuclear gene (c-mos), we explored the relationships within the Asian pit viper genus Gloydius. In total, 23 samples representing 10 species were analyzed. All phylogenetic analyses support a monophyletic Gloydius with two major clades, one comprising G. brevicaudus, G. blomhoffii, and G. ussuriensis with the sister clade consisting of G. intermedius, G. saxatilis, G. halys and G. shedaoensis. The relationships among the three montane species G. strauchi, G. qinlingensis and G. liupanensis, as well as the two monophyletic groups, are unstable, and discussed. Divergence date estimation indicates that Gloydius lineage formed 15 Ma and diversification of the genus occurred at 9.89 Ma. Issues regarding the taxonomy of this genus are discussed where necessary.

A new snake species of the genus Gonyosoma Wagler,1828(Serpentes:Colubridae)from Hainan Island,China

A new species of the genus Gonyosoma Wagler,1828 is described herein based on six specimens from the Diaoluoshan Mountains,Hainan Island,Hainan Province,China.The new species,Gonyosoma hainanense sp.nov.,is most similar to its continental sister species,Gonyosoma boulengeri(Mocquard,1897).Both taxa have a scaled protrusion on the anterior portion of the rostrum,distinct from other congeners.However,Gonyosoma hainanense sp.nov.can be distinguished from G.boulengeri by two significant morphological characters:(1)black orbital stripe absent in adults(vs.present in G.boulengeri);and(2)two loreals(vs.one loreal in G.boulengeri).The new species is also genetically divergent and forms a unique clade from its sister species and all other congeners based on sequences of the mitochondrial gene cytochrome b(cyt b).

The Utility of 1000 - 500 mb Thickness and Weather Type as a Rain-Snow Divide: A 30-Year Study at Albany, NY

Winter synoptic conditions that produce snowfall with bitterly cold temperatures create both social and economic hazards in the capital city of Albany, NY. Sometimes these systems are forecasted in error to produce rain or mixed precipitation. It is beneficial for meteorologists to better understand the commonly used 5400 and 1300 GPM line to better forecast rain versus snow events. Other studies have looked into the use of the 5400 GPM (540 dm) line but none have assessed the validity of this boundary with respect to weather type characterization at Albany. This study aims to determine the reliability of the widely referenced guides for depicting the rain-snow line, and improve forecast aids for the vertical atmosphere during winter precipitation events. The mean daily 500, 850, 925 and 1000 mb heights and weather type frequency of the Spatial Synoptic Classification between November and March of 1980 - 2012 are analyzed. Results indicate that the standard vertical boundaries are inaccurate indicators of a rain versus snow event in Albany. More reasonable rain-snow cut offs for the 1000 - 500 and 1000 - 850 mb thicknesses are 5222 and 1262 GPM. For the 1000 - 925 mb level, 606 GPM is a helpful aid of identifying the rain-snow boundary. Further scrutinizing by weather type indicates that the rain-snow boundary also varies depending on what air mass/weather type is present on a given day. For instance, when the most prominent weather type is observed over Albany (Dry Polar), at the 1000 - 850 mb and 1000 - 500 mb layers, a boundary of 1242 GPM and 5152 GPM is found to be most representative. Results indicate only for the rarest of winter weather types observed over Albany, Moist Tropical, are the standard cut offs useful. Determining the reliability of this precipitation indicator at a specific station, like Albany, could enable meteorologists in other regions of the country to draw parallels between weather type, precipitation, and thickness in their forecast zones.

Temporary coronary sinus pacing to improve ventricular dyssynchrony with cardiogenic shock: A case report

BACKGROUND Temporary transvenous pacing through the coronary sinus is a novel approach rarely used in treating unstable bradycardia.This modality could provide cardiac pacing while achieving better ventricular synchrony.We present a case who received cardiac pacing through the coronary sinus and provide a summary of evidence in the current literature.CASE SUMMARY A 55-year-old woman with a history of advanced heart failure was admitted to the rehabilitation ward after a recent stroke.During hospitalization,she had paroxysmal atrial fibrillation with rapid ventricular response resulting from fluid overload.While atrial fibrillation was spontaneously reversed to sinus rhythm after diuresis,she developed multiple episodes of polymorphic ventricular tachycardia along with sinus bradycardia and prolonged QTc interval.She became hypotensive despite appropriate medical management.Pacing through her implantable cardioverter-defibrillator was attempted but worsened her hypotension.Ventricular dyssynchrony was suspected.Temporary transvenous atrial pacing through the coronary sinus was performed,which stabilized her blood pressure and improved end-organ perfusion.A permanent biventricular pacemaker was later implanted,and she was safely discharged to a nursing home.CONCLUSION Temporary transvenous pacing through the coronary sinus,a novel approach to treat unstable bradycardia,may reduce ventricular dyssynchrony.

Contribution of Sumalindo Company:In Managing Forest Resources with Local Communities:Mahakam Ulu-East Kalimantan

The role of HPH(Forest Logging Concession)in developing rural communities is very significant.SLJ(Sumalindo Lestari Jaya)as HPH company has an important contribution in empowering local communities,especially in opening land transportation in the interior and helping to build agriculture and gardens.The existence of Sumalindo company participates in developing forest resource management with local communities,among others,increasing livelihoods,maintaining and developing biodiversity conservation and maintaining climate change.These efforts are in accordance with the regulations of the KLHK(Ministry of Environment and Forestry),that every HPH holder is required(mandatory)to obtain a certificate of“PHAPL”(Sustainable Production Natural Forest Management)and an“eco label”from the Indonesian Eco Label Institute.Besides,it is recommended that the holders of HPH concessions and HTI(Industrial Timber Plantations)have an FSC(Forest Stewardship Council)certificate from the EU(European Union),and must meet three indicator elements,namely economic,social and ecological in SFM(Sustainable Forest Management).This article examines three critical questions that show the role of Sumalindo Company in economic,ecological and social development and managing forest resources with the community as follows:(1)The role of Sumalindo company contributes to the development of road infrastructure in the interior;(2)The role of Sumalindo in improving livelihoods and economic and social empowerment of local communities;(3)The role of Sumalindo with local communities in managing forest resources,including maintaining and developing biodiversity conservation and maintaining climate change.

Mitogenomic phylogeny of the Asian colobine genus Trachypithecus with special focus on Trachypithecus phayrei(Blyth, 1847) and description of a new species

Trachypithecus,which currently contains 20 species divided into four groups,is the most speciose and geographically dispersed genus among Asian colobines.Despite several morphological and molecular studies,however,its evolutionary history and phylogeography remain poorly understood.Phayre’s langur(Trachypithecus phayrei) is one of the most widespread members of the genus,but details on its actual distribution and intraspecific taxonomy are limited and controversial.Thus,to elucidate the evolutionary history of Trachypithecus and to clarify the intraspecific taxonomy and distribution of T.phayrei,we sequenced 41 mitochondrial genomes from georeferenced fecal samples and museum specimens,including two holotypes.Phylogenetic analyses revealed a robustly supported phylogeny of Trachypithecus,suggesting that the T.pileatus group branched first,followed by the T.francoisi group,and the T.cristatus and T.obscurus groups most recently.The four species groups diverged from each other 4.5-3.1 million years ago(Ma),while speciation events within these groups occurred much more recently(1.6-0.3 Ma).Within T.phayrei,we found three clades that diverged 1.0-0.9 Ma,indicating the existence of three rather than two taxa.Following the phylogenetic species concept and based on genetic,morphological,and ecological differences,we elevate the T.phayrei subspecies to species level,describe a new species from central Myanmar,and refine the distribution of the three taxa.Overall,our study highlights the importance of museum specimens and provides new insights not only into the evolutionary history of T.phayrei but the entire Trachypithecus genus as well.

Back to the future:Some similarities and many differences between autism spectrum disorder and early onset schizophrenia.Clues to pathophysiology?

In the first issue of the recently launched journal,Medicine Plus,Lu et al.[1]report on a remarkable effort encompassing nearly 600 young participants examined at five centers in China.The focus was on the first episode early-onset schizophrenia(EOS;onset before age 18 years)and autism spectrum disorder(ASD),contrasted to each other and healthy controls(HC).Historically,autism was initially considered a form of infantile schizophrenia,although it was differentiated from early-onset schizophrenia as early as 1955 by Eisenberg and Kanner[2].

Sirt5 desuccinylates Cdc42 to mediate osteoclastogenesis and bone remodeling in mice

Post-translational modifications(PTMs)play a critical role in bone remodeling,with phosphorylation and acetylation being particularly well characterized.Recently,succinylation,a relatively uncommon PTM on lysine,has received considerable research attention for its influence on several physiological and pathological processes and conditions.1 Several substrates involved in mitochondrial pathways have been validated as substrates for the desuccinylase sirtuin 5(Sirt5),a key regulator of succinylation.2 Bone is one of the most metabolically active organs,but the role of succinylation during bone remodeling is not well characterized.

Arabidopsis ABCG14 forms a homodimeric transporter for multiple cytokinins and mediates long-distance transport of isopentenyladeninetype cytokinins

Cytokinins(CKs),primarily trans-zeatin(tZ)and isopentenyladenine(iP)types,play critical roles in plant growth,development,and various stress responses.Long-distance transport of tZ-type CKs meidated by Arabidopsis ATP-binding cassette transporter subfamily G14(AtABCG14)has been well studied;however,less is known about the biochemical properties of AtABCG14 and its transporter activity toward iP-type CKs.Here we reveal the biochemical properties of AtABCG14 and provide evidence that it is also required for long-distance transport of iP-type CKs.AtABCG14 formed homodimers in human(Homo sapiens)HEK293T,tobacco(Nicotiana tabacum),and Arabidopsis cells.Transporter activity assays of AtABCG14 in Arabidopsis,tobacco,and yeast(Saccharomyces cerevisiae)showed that AtABCG14 may directly transport multiple CKs,including iP-and tZ-type species.AtABCG14 expression was induced by iP in a tZ-type CKdeficient double mutant(cypDM)of CYP735A1 and CYP735A2.The atabcg14 cypDM triple mutant exhibited stronger CK-deficiency phenotypes than cypDM.Hormone profiling,reciprocal grafting,and 2H6-iP isotope tracer experiments showed that root-to-shoot and shoot-to-root long-distance transport of iP-type CKs were suppressed in atabcg14 cypDM and atabcg14.These results suggest that AtABCG14 participates in three steps of the circular long-distance transport of iP-type CKs:xylem loading in the root for shootward transport,phloem unloading in the shoot for shoot distribution,and phloemunloading in the root for root distribution.We found that AtABCG14 displays transporter activity toward multiple CK species and revealed its versatile roles in circular long-distance transport of iP-type CKs.These findings provide newinsights into the transport mechanisms of CKs and other plant hormones.

图书情报领域中外学者研究方法使用差异分析——跨语言文本分类的视角

[目的/意义]对学科研究方法的自省式分析对于理解学科发展和建立学科自主知识体系至关重要。通过研究国内外学者在研究方法上的使用差异,可以更全面地了解不同地区和文化背景下的研究者在应对不同研究问题所采用的策略和方法,从而促进学术交流和跨国合作,并进一步推动学科的发展与学科知识体系的完善。[方法/过程]以图书情报领域5种高影响力中英文期刊中1990-2021年共30余年的学术论文为研究对象,采用跨语言文本分类方法对这些论文中的研究方法进行自动分类。然后从研究方法的使用频率与演化差异以及适用主题多样性差异两个角度,进行中外比较研究。[结果/结论]国外学者越来越倾向于使用定性方法,而对定量方法的使用正在减少。同时,国内外大多数研究方法的适用主题多样性都在增加。这项研究对于理解图书情报学科的发展、促进学术交流与合作以及提高国内学者的国际影响力具有重要意义。

户外坐席系统设计要素研究

户外坐席形式在各类户外空间中广泛存在,但其设计理论未有深入研究。文章通过设计实践与考察调研、文献辅助,用系统论方法,将设计系统的“人、事、场、物”作为系统单元要素为理论推演,回归人为事物的“人、事、场、物”基本要素框架,对户外坐席系统设计要素进行分析,明确户外坐席的系统设计要素内容,为其系统设计及后续研究明确方向。

Comparative analysis of 12 water lily plastid genomes reveals genomic divergence and evolutionary relationships in early flowering plants

The aquatic plant Nymphaea,a model genus of the early flowering plant lineage Nymphaeales and family Nymphaeaceae,has been extensively studied.However,the availability of chloroplast genome data for this genus is incomplete,and phylogenetic relationships within the order Nymphaeales remain controversial.In this study,12 chloroplast genomes of Nymphaea were assembled and analyzed for the first time.These genomes were 158,290-160,042 bp in size and contained 113 non-repeat genes,including 79 protein-coding genes,30 tRNA genes,and four rRNA genes.We also report on codon usage,RNA editing sites,microsatellite structures,and new repetitive sequences in this genus.Comparative genomics revealed that expansion and contraction of IR regions can lead to changes in the gene numbers.Additionally,it was observed that the highly variable regions of the chloroplast genome were mainly located in intergenic regions.Furthermore,the phylogenetic tree showed the order Nymphaeales was divided into three families,and the genus Nymphaea can be divided into five(or three)subgenera,with the subgenus Nymphaea being the oldest.The divergence times of nymphaealean taxa were analyzed,with origins of the order Nymphaeales and family Nymphaeaceae being about 194 and 131 million years,respectively.The results of the phylo-genetic analysis and estimated divergence times will be useful for future evolutionary studies of basal angiosperm lineages.

红树林沉积物聚乙烯降解菌的筛选和降解特性

【目的】探究湛江市麻章区红树林沉积物中微生物对聚乙烯(PE)塑料的降解特性,丰富红树林塑料降解菌种类。【方法】在湛江市麻章区红树林的高、中、低潮带随机选取9个样点,并采用五点采样法从红树林表层2~5 cm的沉积物中取样。将采集到的沉积物样本在以聚乙烯为唯一碳源的无机盐培养基中进行富集、分离、纯化,以筛选出能够降解PE的菌株,并通过显微形态分析、分子鉴定等方法确定其种属;通过测定生长曲线、失重率、以及分析官能团变化来验证菌株对PE塑料的降解性能。【结果与结论】从沉积物中共筛选出K1-1、K1-2和K1-3三株PE降解能力较强的菌,分别为威尼斯不动杆菌(Acinetobacter venetianus)、Pseudomonas juntendi和维德曼芽孢杆菌(Bacillus wiedmannii)。在120 d的培养周期中,这些菌株的生长曲线均呈抛物线形态。经三株菌作用后,PE表面生成羟基,并形成氨基和羟基化合物,羟基取代羰基,导致PE表观和内部结构明显改变。经120 d处理后,PE膜的失重率分别为6.42%、5.38%和5.73%,其中K1-1菌株处理后PE塑料的失重率相较于目前报道的红树林沉积物中最高降解效率菌株Bacillus gottheilii处理后塑料的失重率提升3.55%。威尼斯不动杆菌(A.venetianus)在PE塑料降解上具有一定潜力,这丰富了湛江红树林沉积物中PE降解菌的种类,为PE塑料的生物降解提供理论支持。