New Isopropyl Chromone and Flavanone Glucoside Compounds from the Leaves of Syzygium cerasiforme (Blume) Merr. & L.M.Perry and Their Inhibition of Nitric Oxide Production

A new isopropyl chromone ( 1 ) and a new flavanone glucoside ( 2 ) together with eleven known compounds ( 3–13 ) were isolated from the leaves of Syzygium cerasiforme (Blume) Merr. & L.M.Perry. Their structures were elucidated as 5,7-dihydroxy-2-isopropyl-6,8-dimethyl-4H-chromen-4-one ( 1 ), 5,7-dihydroxyflavanone 7-O-β-D-(6′′-O-galloylglucopyranoside) ( 2 ), strobopinin ( 3 ), demethoxymatteucinol ( 4 ), pinocembrin-7-O-β-D-glucopyranoside ( 5 ), (2S)-hydroxynaringenin-7-O-β-D-glucopyranoside ( 6 ), afzelin ( 7 ), quercetin ( 8 ), kaplanin ( 9 ), endoperoxide G3 ( 10 ), grasshopper ( 11 ), vomifoliol ( 12 ), litseagermacrane ( 13 ) by the analysis of HR-ESI-MS, NMR, and CD spectral data. Compounds 1 , 2 , 5 , 6 and 10 inhibited NO production on LPS-activated RAW264.7 cells with IC₅₀ values of 12.28±1.15, 8.52±1.62, 7.68±0.87, 9.67±0.57, and 6.69±0.34 μM, respectively, while the IC₅₀ values of the other compounds ranging from 33.38±0.78 to 86.51±2.98 μM, compared to that of the positive control, N^G-monomethyl-L-arginine acetate (L-NMMA) with an IC₅₀ value of 32.50±1.00 μM.     

Human erythroid cells produced ex vivo at large scale differentiate into red blood cells in vivo

New sources of red blood cells (RBCs) would improve the transfusion capacity of blood centers. Our objective was to generate cells for transfusion by inducing a massive proliferation of hematopoietic stem and progenitor cells, followed by terminal erythroid differentiation. We describe here a procedure for amplifying hematopoietic stem cells (HSCs) from human cord blood (CB) by the sequential application of specific combinations of growth factors in a serum-free culture medium. The procedure allowed the ex vivo expansion of CD34+ progenitor and stem cells into a pure erythroid precursor population. When injected into nonobese diabetic, severe combined immunodeficient (NOD/SCID) mice, the erythroid cells were capable of proliferation and terminal differentiation into mature enucleated RBCs. The approach may eventually be useful in clinical transfusion applications.     

Oxide-Based Solid-State Batteries: A Perspective on Composite Cathode Architecture

The garnet-type phase Li₇La₃Zr₂O₁₂ (LLZO) attracts significant attention as an oxide solid electrolyte to enable safe and robust solid-state batteries (SSBs) with potentially high energy density. However, while significant progress has been made in demonstrating compatibility with Li metal, integrating LLZO into composite cathodes remains a challenge. The current perspective focuses on the critical issues that need to be addressed to achieve the ultimate goal of an all-solid-state LLZO-based battery that delivers safety, durability, and pack-level performance characteristics that are unobtainable with state-of-the-art Li-ion batteries. This perspective complements existing reviews of solid/solid interfaces with more emphasis on understanding numerous homo- and heteroionic interfaces in a pure oxide-based SSB and the various phenomena that accompany the evolution of the chemical, electrochemical, structural, morphological, and mechanical properties of those interfaces during processing and operation. Finally, the insights gained from a comprehensive literature survey of LLZO–cathode interfaces are used to guide efforts for the development of LLZO-based SSBs.     

Alternative approach to generate shRNA from cDNA

Short hairpin RNA (shRNA) synthesized from vector-based expression is as effective as short interfering RNA (siRNA) synthesized in vitro for suppressing the expression of their corresponding genes. Recently, three groups independently reported a new technology to construct an shRNA library from cDNA, providing great hope for genome-wide functional screens in many biological systems. In the present study, we report an alternative approach to generate shRNA from cDNA. A major improvement was to use a nicking enzyme to open up the double-stranded DNA so that the loop region remains single-stranded while the rest of the DNA fragment is double-stranded at an elevated temperature (e.g., 72 degrees C). The single-stranded DNA was then converted into double-stranded DNA by Taq DNA polymerase using the existing strand in the double-stranded region as a primer. Thus, the extended product carried a palindromic structure of 19 bp separated by a loop. Finally, the DNA fragment was cloned into a vector that carries an H1 promoter at the upstream region and ends with 5Ts, a terminator for the Pol III polymerase, at the downstream region. To prove the principle, we constructed shRNA from green fluorescent protein (GFP) cDNA and successfully suppressed GFP expression. Consequently, this simplified approach provides a better alternative to generate shRNA libraries from cDNA. Such shRNA libraries can be used to identify potential siRNA target sequences and study gene functions by a variety of selection methods.     

The impact of interventions in the global land and agri‐food sectors on Nature’s Contributions to People and the UN Sustainable Development Goals

Interlocked challenges of climate change, biodiversity loss, and land degradation require transformative interventions in the land management and food production sectors to reduce carbon emissions, strengthen adaptive capacity, and increase food security. However, deciding which interventions to pursue and understanding their relative co‐benefits with and trade‐offs against different social and environmental goals have been difficult without comparisons across a range of possible actions. This study examined 40 different options, implemented through land management, value chains, or risk management, for their relative impacts across 18 Nature's Contributions to People (NCPs) and the 17 Sustainable Development Goals (SDGs). We find that a relatively small number of interventions show positive synergies with both SDGs and NCPs with no significant adverse trade‐offs; these include improved cropland management, improved grazing land management, improved livestock management, agroforestry, integrated water management, increased soil organic carbon content, reduced soil erosion, salinization, and compaction, fire management, reduced landslides and hazards, reduced pollution, reduced post‐harvest losses, improved energy use in food systems, and disaster risk management. Several interventions show potentially significant negative impacts on both SDGs and NCPs; these include bioenergy and bioenergy with carbon capture and storage, afforestation, and some risk sharing measures, like commercial crop insurance. Our results demonstrate that a better understanding of co‐benefits and trade‐offs of different policy approaches can help decision‐makers choose the more effective, or at the very minimum, more benign interventions for implementation.     

Isolation of New Delhi metallo‐β‐lactamase 1‐producing Vibrio cholerae non‐O1, non‐O139 strain carrying ctxA,st and hly genes in southern Vietnam

Vibrio cholerae non‐O1, non‐O139 (VC_NAG) organisms are universally present in the aquatic environment and regarded as non‐pathogenic bacteria. However, considering that they do occasionally induce gastroenteritis, a study of their virulence and antibiotic resistance genes is important. The presence of enteropathogenic genes, including ctxA, VC_NAG‐specific heat‐stable toxin gene (st), hemolysin (hly), and zona occludens toxin (zot) was determined by PCR in 100 VC_NAG strains isolated in southern Vietnam in 2010–2013 from 94 environmental and six human origins. These 100 VC_NAG strains were also tested phenotypically and genotypically for the presence of the New Delhi metallo‐β‐lactamase (NDM‐1). Of the 100 VC_NAG strains tested, six were positive for ctxA; five from the environment and one of human origin. The st gene was detected in 17 isolates, 15 and two of which were of environmental and human origins, respectively. Gene hly was detected in 19 VC_NAG strains examined, two of which were isolated from humans and 17 from environments. The zot gene was not detected in any of the strains tested. Three VC_NAG strains of environmental origin were confirmed to produce NDM‐1 and the bla_NDM‐1 gene was detected in those strains by PCR. Of note, one of the three NDM‐1‐producing VC_NAG strains was confirmed to carry ctxA, st and hly genes concurrently. This is the first report of isolation of NDM‐1‐producing VC_NAG strains in Vietnam.     

Prevalence,Awareness, Treatment,and Control of High Blood Pressure: A Population-Based Survey in Thai Nguyen,Vietnam

Background

Cardiovascular disease (CVD) is one of the leading causes of morbidity and mortality in Vietnam and hypertension (HTN) is an important and prevalent risk factor for CVD in the adult Vietnamese population. Despite an increasing prevalence of HTN in this country, information about the awareness, treatment, and control of HTN is limited. The objectives of this study were to describe the prevalence, awareness, treatment, and control of HTN, and factors associated with these endpoints, in residents of a mountainous province in Vietnam.

Methods

Data from 2,368 adults (age≥25 years) participating in a population-based survey conducted in 2011 in Thai Nguyen province were analyzed. All eligible participants completed a structured questionnaire and were examined by community health workers using a standardized protocol.

Results

The overall prevalence of HTN in this population was 23%. Older age, male sex, and being overweight were associated with a higher odds of having HTN, while higher educational level was associated with a lower odds of having HTN. Among those with HTN, only 34% were aware of their condition, 43% of those who were aware they had HTN received treatment and, of these, 39% had their HTN controlled.

Conclusions

Nearly one in four adults in Thai Nguyen is hypertensive, but far fewer are aware of this condition and even fewer have their blood pressure adequately controlled. Public health strategies increasing awareness of HTN in the community, as well as improvements in the treatment and control of HTN, remain needed to reduce the prevalence of HTN and related morbidity and mortality.     

A Prognostic Model for Development of Profound Shock among Children Presenting with Dengue Shock Syndrome

PurposeTo identify risk factors and develop a prediction model for the development of profound and recurrent shock amongst children presenting with dengue shock syndrome (DSS)MethodsWe analyzed data from a prospective cohort of children with DSS recruited at the Paediatric Intensive Care Unit of the Hospital for Tropical Disease in Ho Chi Minh City, Vietnam. The primary endpoint was “profound DSS”, defined as ≥2 recurrent shock episodes (for subjects presenting in compensated shock), or ≥1 recurrent shock episodes (for subjects presenting initially with decompensated/hypotensive shock), and/or requirement for inotropic support. Recurrent shock was evaluated as a secondary endpoint. Risk factors were pre-defined clinical and laboratory variables collected at the time of presentation with shock. Prognostic model development was based on logistic regression and compared to several alternative approaches.ResultsThe analysis population included 1207 children of whom 222 (18%) progressed to “profound DSS” and 433 (36%) had recurrent shock. Independent risk factors for both endpoints included younger age, earlier presentation, higher pulse rate, higher temperature, higher haematocrit and, for females, worse hemodynamic status at presentation. The final prognostic model for “profound DSS” showed acceptable discrimination (AUC=0.69 for internal validation) and calibration and is presented as a simple score-chart.ConclusionsSeveral risk factors for development of profound or recurrent shock among children presenting with DSS were identified. The score-chart derived from the prognostic models should improve triage and management of children presenting with DSS in dengue-endemic areas.     

CD33‐targeting extracellular vesicles deliver antisense oligonucleotides against FLT3‐ITD and miR‐125b for specific treatment of acute myeloid leukaemia

IntroductionAcute Myeloid Leukaemia (AML) is the most common blood cancer in adults. Although 2 out of 3 AML patients go into total remission after chemotherapies and targeted therapies, the disease recurs in 60%–65% of younger adult patients within 3 years after diagnosis with a dramatically decreased survival rate. Therapeutic oligonucleotides are promising treatments under development for AML as they can be designed to silence oncogenes with high specificity and flexibility. However, there are not many well validated approaches for safely and efficiently delivering oligonucleotide drugs. This issue could be resolved by utilizing a new generation of delivery vehicles such as extracellular vesicles (EVs).MethodsIn this study, we harness red blood cell‐derived EVs (RBCEVs) and engineer them via exogenous drug loading and surface functionalization to develop an efficient drug delivery system for AML. Particularly, EVs are designed to target CD33, a common surface marker with elevated expression in AML cells via the conjugation of a CD33‐binding monoclonal antibody onto the EV surface.ResultsThe conjugation of RBCEVs with the CD33‐binding antibody significantly increases the uptake of RBCEVs by CD33‐positive AML cells, but not by CD33‐negative cells. We also load CD33‐targeting RBCEVs with antisense oligonucleotides (ASOs) targeting FLT3‐ITD or miR‐125b, 2 common oncogenes in AML, and demonstrate that the engineered EVs improve leukaemia suppression in in vitro and in vivo models of AML.ConclusionTargeted RBCEVs represent an innovative, efficient, and versatile delivery platform for therapeutic ASOs and can expedite the clinical translation of oligonucleotide drugs for AML treatments by overcoming current obstacles in oligonucleotide delivery.

In this study, we harness red blood cell‐derived EVs (RBCEVs) and engineer them with surface functionalization and exogenous drug loading to develop an efficient drug delivery system for AML. Anti‐CD33 antibody was conjugated to RBCEVs using an enzymatic method combined with the streptavidin‐biotin system. We load the antibody conjugated RBCEVs with ASOs targeting FLT3‐ITD or miR‐125b, 2 common oncogenes in AML, and demonstrate that the treatment with engineered EVs improve leukaemia suppression both in vitro and in vivo.     

越南苦苣苔科石蝴蝶属植物随记暨国家级分布新记录

石蝴蝶属(Petrocosmea Oliv.)植物的现代分布与分化中心位于中国的西南山地以及周边国家和地区,如印度(阿萨姆邦)、缅甸、泰国、越南等也有分布。近年来,中国和中南半岛上各个国家和地区的新分类群和国家级新记录层出不穷,进一步加深了研究人员对中国和中南半岛植物区系以及该属植物在上述区域的多样性的理解。例如,滇黔石蝴蝶[Petrocosmea martinii (H. Léveillé)H. Léveillé]和丝毛石蝴蝶(P. sericea C.Y. Wu ex H. W. Li)曾被认为是中国的特有种,前者分布于贵州、广西北部和云南东南部,而后者仅见于云南东南部。该文报道了这两种石蝴蝶属植物的越南国家级分布新记录。这两个新记录种的发现,使得越南分布的石蝴蝶属植物种的数量上升到了5 种,这些新记录种的报道或暗示未来在与中国西南山地邻近的地区还将会有更多该属的新分类群或新记录有待发现。该文还同时提供了这两个国家级分布新记录物种的描述、图示、濒危等级现状评价以及目前所有越南已知分布的石蝴蝶属植物的检索表以备检索和核对。