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Alzheimer's disease (AD) is rapidly reaching epidemic proportions in the United States, currently affecting more than 5 million individuals and predicted to affect 14 million by 2050. Despite a general consensus that the amyloid-beta (Abeta) protein plays a significant role in disease progression, the underlying pathology of the disease is not entirely clear. Caenorhabditis elegans is a simple organism that has been used as a model for basic mechanistic studies on the underlying pathological processes involved in AD. Previous studies from our labs demonstrated that transgenic C. elegans with muscle specific expression of human Abeta undergo rapid paralysis, and worms with neuronal expression of Abeta show deficits in chemotaxis to volatile chemicals. In this study, we evaluate the effect of neuron specific expression of Abeta on multiple neuronally controlled behaviors in a transgenic C. elegans. These worms demonstrate deficits in odorant preference associative learning behavior, and the serotonin-controlled behaviors experience-dependent learning and egg laying. These newly identified learning-deficit behavioral phenotypes in the neuronal Abeta C. elegans suggest that the model may be used to elucidate underlying pathological events related to development of AD and for pharmaceutical intervention. [ABSTRACT FROM AUTHOR]

By opting for this effective alternative to I.V. therapy, you can spare your elderly patients the stress of venipuncture. [ABSTRACT FROM AUTHOR]

Rigid bicyclic hydrocarbons have emerged as important building blocks in the drug discovery industry. Despite progress in this general area, bicyclo[2.1.0]pentanes (housanes) are an understudied class of molecules. Herein we report an unconventional synthesis of borylated housanes. Our method features a broad scope and high diastereoselectivities in the synthesis of versatile intermediates. The route involves a strain-release diboration of bicyclo[1.1.0]butane and intramolecular deborylative alkylation. The versatility of the bridgehead boronic ester was demonstrated in several functionalizations. Lastly, the mechanism of the reaction was investigated, and an unusual stereospecific and diastereoselective ring expansion was uncovered.

A strategy for the photosensitized [2+2]-cycloaddition between styrenyl dihaloboranes and unactivated allylamines to access cyclobutylboronates with control of stereochemistry and regiochemistry is presented. The success of the reaction relies on the temporary coordination between in situ generated dihaloboranes and amines under mild reaction conditions. In addition, cyclobutanes with varying substitution patterns have been prepared using N-heterocycles as directing group. Manipulation of the C-B bond allows for the synthesis of a diverse class of cyclobutanes from simple precursors. Moreover, these reactions lead to the synthesis of complex amines and heteroaromatic compounds, which have significant utility in medicinal chemistry. Finally, a dearomative [4+2]-cycloaddition of naphthalenes using a boron-enabled temporary tethering strategy has also been uncovered to synthesize complex 3-dimensional borylated building blocks., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Radioimmunotherapy (RIT) with α-particle-emitting, 225 Ac complexed to trastuzumab may offer an alternative treatment for patients who progress on HER2-targeted therapies. Moreover, RIT with [ 225 Ac]Ac-DOTA-trastuzumab could be combined with SPECT/CT imaging with [ 111 In]In-DOTA-trastuzumab in a theranostic approach. In this study, we compared DOTA-conjugated trastuzumab IgG, F(ab') 2 or Fab complexed to 111 In or 225 Ac for SPECT/CT imaging and α-particle RIT of subcutaneous (s.c.) HER2-positive 164/8-1B/H2N.luc + human BC tumors in NRG mice. SPECT/CT imaging and tumor and normal tissue uptake were compared in NRG or NOD-SCID mice coinjected i.v. with [ 111 In]In-DOTA-trastuzumab IgG, F(ab') 2 or Fab and [ 225 Ac]Ac-DOTA-trastuzumab IgG, F(ab') 2 or Fab. Radiation absorbed doses in the tumor and normal organs for [ 225 Ac]Ac-DOTA-trastuzumab IgG, F(ab') 2 or Fab were estimated based on the biodistribution of the [ 111 In]In-DOTA-trastuzumab IgG, F(ab') 2 or Fab. Normal tissue toxicity was assessed by hematology and blood biochemistry analyses and monitoring body weight in NRG mice injected i.v. with 2 and 4 kBq of [ 225 Ac]Ac-DOTA-trastuzumab IgG, F(ab') 2 or Fab separated by 8 d. RIT studies were performed in NRG mice with s.c. 164/8-1B/H2N.luc + tumors injected i.v. with 2 kBq and 4 kBq of [ 225 Ac]Ac-DOTA-trastuzumab IgG, F(ab') 2 or Fab separated by 8 d or irrelevant [ 225 Ac]Ac-DOTA-IgG 1 , two doses of unlabeled trastuzumab IgG or 0.9% NaCl. A tumor growth index (TGI) was plotted vs time (d) and Kaplan-Meier median survival estimated. [ 111 In]In-DOTA-trastuzumab IgG or F(ab') 2 exhibited 4.1-fold and 3.3-fold significantly greater tumor uptake at 2 d postinjection (p.i.) than Fab at 24 h p.i. However, spleen uptake at 2 d p.i. for [ 111 In]In-DOTA-trastuzumab IgG was 3.3-fold significantly higher than F(ab') 2 and 13.2-fold higher than Fab at 24 h p.i. [ 111 In]In-DOTA-trastuzumab F(ab') 2 and Fab exhibited higher kidney uptake than IgG. Tumors were imaged by SPECT/CT with [ 111 In]In-DOTA-trastuzumab IgG and F(ab') 2 but were not well-visualized with [ 111 In]In-DOTA-trastuzumab Fab. The absorbed dose in the tumor was 2.2-fold greater for [ 225 Ac]Ac-DOTA-trastuzumab F(ab') 2 than IgG and 3.4-fold greater than Fab. Hematological toxicity was observed for [ 225 Ac]Ac-DOTA-trastuzumab IgG but not for [ 225 Ac]Ac-DOTA-trastuzumab F(ab') 2 or Fab. No kidney or liver toxicity or decreased body weight was observed for any RIT agent. Tumor growth was significantly inhibited by [ 225 Ac]Ac-DOTA-trastuzumab IgG, F(ab') 2 or Fab but [ 225 Ac]Ac-DOTA-trastuzumab F(ab') 2 was most effective for increasing median survival (46 d vs 22 d for IgG and 29 d for Fab). We conclude that [ 111 In]In- and [ 225 Ac]Ac-DOTA-trastuzumab F(ab') 2 exhibited superior properties for theranostic imaging and α-particle RIT of HER2-positive human BC xenografts in NRG mice.

Introduction: Our objective was to study convection enhanced delivery (CED) of 177 Lu-labeled metal chelating polymer (MCP) conjugated to gold nanoparticles ([ 177 Lu]Lu-MCP-AuNP) alone or combined with anti-PD1 immune checkpoint inhibition (ICI) for improving the survival of immunocompetent C57BL/6J mice with orthotopic GL261 murine glioma tumors., Methods: C57BL/6J mice with GL261 tumors were treated with [ 177 Lu]Lu-MCP-AuNP (0.8 or 2.7 MBq; 4 × 10 11 AuNP) alone or combined with anti-PD1 antibodies (200 μg i.p. every 2 d × 3 doses). Control mice received normal saline, non-radioactive MCP-AuNP or anti-PD1 antibodies. Kaplan-Meier median survival was estimated. T-cell infiltration into the brain was probed by flow cytometry. Toxicity was assessed by monitoring body weight and cognitive function tests [Object Location Test (OLT) and Novel Object Recognition Test (NORT)] and T2-weighted MRI of the brain, overall health and ex vivo histopathological examination of the brain., Results: Treatment with [ 177 Lu]Lu-MCP-AuNP (0.8 MBq) significantly increased median survival compared to MCP-AuNP (29 vs. 25 d; P = 0.007) or normal saline-treated mice (24 d; P < 0.001). Combining [ 177 Lu]Lu-MCP-AuNP (0.8 MBq) with anti-PD1 antibodies increased median survival to 32 d (P < 0.0001 vs. normal saline). Increasing the mean amount of [ 177 Lu]Lu-MCP-AuNP to 2.7 MBq and combining with anti-PD1 antibodies extended survival to at least 218 d in 5/9 mice. Increased CD8 + cytotoxic T-cells and decreased CD4 + helper T-cells were found in the brain vs. normal saline-treated mice. No weight loss (>20 %) was observed for treated or control mice. There was no change in cognitive function in mice treated with [ 177 Lu]Lu-MCP-AuNP (0.8 MBq) alone or combined with anti-PD1 antibodies assessed by the OLT or NORT. T2-weighted MRI in mice treated with 2.7 MBq [ 177 Lu]Lu-MCP-AuNP combined with anti-PD1 antibodies revealed edema, gliosis and ex vacuo dilatation of the ventricle proximal to the site of infusion. Histopathological examination of the brain revealed dilatation of the ventricle and gliosis proximal to the site of infusion but no radiation necrosis. MRI and histological analysis did not reveal tumor in the brain of these mice. Mice treated with 2.7 MBq [ 177 Lu]Lu-MCP-AuNP combined with anti-PD1 antibodies did not demonstrate overall deleterious health effects., Conclusions: We conclude that CED of [ 177 Lu]Lu-MCP-AuNP combined with anti-PD1 checkpoint immunotherapy improved the survival of immunocompetent C67BL/6J mice with GL261 glioma tumors in the brain. Higher administered amounts of [ 177 Lu]Lu-MCP-AuNP (2.7 MBq vs. 0.8 MBq) were most effective and yielded long-term survival., Advances in Knowledge and Implications for Patient Care: This study demonstrates that combining a locally-infused radiation nanomedicine, [ 177 Lu]Lu-MCP-AuNP and anti-PD1 checkpoint immunotherapy improved the survival of mice with glioma tumors in the brain. In the future, this treatment may be useful to treat residual tumor at the surgical margins in patients with GBM to prevent local recurrence and improve survival., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

A new species of Cyanea is described from trawl samples collected in the Gulf of Guinea during 2017 and 2019. The species is a member of the nozakii-group, possessing interrupted radial septa, and is characterised by, inter alia, deeper rhopalial than velar marginal clefts, a uniformly papillose exumbrella, up to 200 tentacles per tentacle cluster and a dense network of anastomosing canals in broadly quadratic lappets. The species can be distinguished genetically from its congeners at both ITS1 and COI (minimum of 14.4% intergroup variation) regions as confirmed by multiple phylogenies and K2P analyses. This is the first record of a nozakii-group member in the Atlantic Ocean and the first description of the genus Cyanea from the west coast of Africa and the tropical Atlantic Ocean.

A strategy for transition metal-free cross-coupling of alkyl nitroso-carbamates and boronic acids is reported. The N-nitroso carbamates are easily prepared from the corresponding amine in two simple steps. This method allows for the synthesis of a wide variety of secondary boronates, benzylic boronates and formal Csp 3 -Csp 2 cross-coupling products under operationally simple conditions. Functional group tolerance is also demonstrated and applied in the modification of lysine to make non-canonical amino acids., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

C-Glycosides are important structures that are common to natural products and pharmaceutical agents. Established methods for their synthesis involve the reaction of an activated anomeric carbon. In this study, we report a conceptually new approach that involves the stereoselective Ni-catalyzed carboboration of glycals. In these reactions, not only is a C-C bond formed at the anomeric carbon, but a synthetically useful C-B bond is also installed. Upon C-B oxidation, differentially protected C-glycosides to be formed. In addition, stereospecific manipulation of the C-B bond leads to diverse C-glycosides. Finally, we report the application of this method in the synthesis of established C-glycosides, such as C-glycosyl amino acids, as well as a strategy to make all possible diastereomers at C1 and C2.

Poor diets are the major cause of death and disease globally, driving high levels of obesity and noncommunicable diseases. Cheap, heavily marketed, ultra-processed, energy-dense and nutrient-poor food and drinks that are high in fat, sugar and salt play a major role. The high-sugar content of these products leads to consumption levels much higher than recommended. The World Health Organization recommends that sugar intake should be reduced to just 5% of energy intake by using fiscal policies and food and drink reformulation strategies. Over the previous decade, the government of the United Kingdom of Great Britain and Northern Ireland has implemented several policies aimed at reducing sugar intake. We compare the soft drinks industry levy and the sugar reduction programme, examining how differences in policy design and process may have influenced the outcomes. Success has been mixed: the mandatory levy achieved a reduction in total sugar sales of 34.3%, and the voluntary reduction programme only achieved a 3.5% reduction in sugar levels of key contributors to sugar intake (despite a target of 20%). Both policies can be improved to enhance their impact, for example, by increasing the levy and reducing the sugar content threshold in the soft drinks industry levy, and by setting more stringent subcategory specific targets in the sugar reduction programme. We also recommend that policy-makers should consider applying a similar levy to other discretionary products that are key contributors to sugar intake. Both approaches provide valuable learnings for future policy in the United Kingdom and globally., ((c) 2024 The authors; licensee World Health Organization.)

Ultra-processed plant-based foods, such as plant-based burgers, have gained in popularity. Particularly in the out-of-home (OOH) environment, evidence regarding their nutritional profile and environmental sustainability is still evolving. Plant-based burgers available at selected OOH sites were randomly sampled in Amsterdam, Copenhagen, Lisbon and London. Plant-based burgers (patty, bread and condiment) ( n 41) were lab analysed for their energy, macronutrients, amino acids and minerals content per 100 g and serving and were compared with reference values. For the plant-based burgers, the median values per 100 g were 234 kcal, 20·8 g carbohydrates, 3·5 g dietary fibre and 12·0 g fat, including 0·08 g TFS and 2·2 g SFA. Protein content was 8·9 g/100 g, with low protein quality according to amino acid composition. Median Na content was 389 mg/100 g, equivalent to 1 g salt. Compared with references, the median serving provided 31% of energy intake based on a 2000 kcal per day and contributed to carbohydrates (17-28%), dietary fibre (42%), protein (40%), total fat (48%), SFA (26%) and Na (54%). One serving provided 15-23% of the reference values for Ca, K and Mg, while higher contributions were found for Zn, Mn, P and Fe (30-67%). The ultra-processed plant-based burgers provide protein, dietary fibre and essential minerals and contain relatively high levels of energy, Na and total fats. The amino acid composition indicated low protein quality. The multifaceted nutritional profile of plant-based burgers highlights the need for manufacturers to implement improvements to better support healthy dietary habits, including reducing energy, Na and total fats.

Background: Radiation nanomedicines are nanoparticles labeled with radionuclides that emit α- or β-particles or Auger electrons for cancer treatment. We describe here our 15 years scientific journey studying locally-administered radiation nanomedicines for cancer treatment. We further present a view of the radiation nanomedicine landscape by reviewing research reported by other groups., Main Body: Gold nanoparticles were studied initially for radiosensitization of breast cancer to X-radiation therapy. These nanoparticles were labeled with 111 In to assess their biodistribution after intratumoural vs. intravenous injection. Intravenous injection was limited by high liver and spleen uptake and low tumour uptake, while intratumoural injection provided high tumour uptake but low normal tissue uptake. Further, [ 111 In]In-labeled gold nanoparticles modified with trastuzumab and injected iintratumourally exhibited strong tumour growth inhibition in mice with subcutaneous HER2-positive human breast cancer xenografts. In subsequent studies, strong tumour growth inhibition in mice was achieved without normal tissue toxicity in mice with human breast cancer xenografts injected intratumourally with gold nanoparticles labeled with β-particle emitting 177 Lu and modified with panitumumab or trastuzumab to specifically bind EGFR or HER2, respectively. A nanoparticle depot (nanodepot) was designed to incorporate and deliver radiolabeled gold nanoparticles to tumours using brachytherapy needle insertion techniques. Treatment of mice with s.c. 4T1 murine mammary carcinoma tumours with a nanodepot incorporating [ 90 Y]Y-labeled gold nanoparticles inserted into one tumour arrested tumour growth and caused an abscopal growth-inhibitory effect on a distant second tumour. Convection-enhanced delivery of [ 177 Lu]Lu-AuNPs to orthotopic human glioblastoma multiforme (GBM) tumours in mice arrested tumour growth without normal tissue toxicity. Other groups have explored radiation nanomedicines for cancer treatment in preclinical animal tumour xenograft models using gold nanoparticles, liposomes, block copolymer micelles, dendrimers, carbon nanotubes, cellulose nanocrystals or iron oxide nanoparticles. These nanoparticles were labeled with radionuclides emitting Auger electrons ( 111 In, 99m Tc, 125 I, 103 Pd, 193m Pt, 195m Pt), β-particles ( 177 Lu, 186 Re, 188 Re, 90 Y, 198 Au, 131 I) or α-particles ( 225 Ac, 213 Bi, 212 Pb, 211 At, 223 Ra). These studies employed intravenous or intratumoural injection or convection enhanced delivery. Local administration of these radiation nanomedicines was most effective and minimized normal tissue toxicity., Conclusions: Radiation nanomedicines have shown great promise for treating cancer in preclinical studies. Local intratumoural administration avoids sequestration by the liver and spleen and is most effective for treating tumours, while minimizing normal tissue toxicity., (© 2024. The Author(s).)

Cardiovascular diseases (CVDs) are the major cause of death among Malaysians. Reduction of salt intake in populations is one of the most cost-effective strategies in the prevention of CVDs. It is very feasible as it requires low cost for implementation and yet could produce a positive impact on health. Thus, salt reduction initiatives have been initiated since 2010, and two series of strategies have been launched. However, there are issues on its delivery and outreach to the target audience. Further, strategies targeting out of home sectors are yet to be emphasized. Our recent findings on the perceptions, barriers and enablers towards salt reduction among various stakeholders including policy-makers, food industries, food operators, consumers and schools showed that eating outside of the home contributed to high salt intake. Foods sold outside the home generally contain a high amount of salt. Thus, this supplementary document is being proposed to strengthen the Salt Reduction Strategy to Prevent and Control Non-communicable Diseases (NCDs) for Malaysia 2021-2025 by focussing on the strategy for the out-of-home sectors. In this supplementary document, the Monitoring, Awareness and Product (M-A-P) strategies being used by the Ministry of Health (MOH) are adopted with a defined outline of the plan of action and indicators to ensure that targets could be achieved. The strategies will involve inter-sectoral and multi-disciplinary approaches, including monitoring of salt intake and educating consumers, strengthening the current enforcement of legislation on salt/sodium labelling and promoting research on reformulation. Other strategies included in this supplementary document included reformulation through proposing maximum salt targets for 14 food categories. It is hoped that this supplementary document could strengthen the current the Salt Reduction Strategy to Prevent and Control NCDs for Malaysia 2021-2025 particularly, for the out-of-home sector, to achieve a reduction in mean salt intake of the population to 6.0 g per day by 2025., (© 2024. The Author(s).)

Saturated bicyclic compounds make up a valuable class of building blocks in the development of agrochemicals and pharmaceuticals. Here, we present the synthesis of borylated bicyclo[2.1.1]hexanes via crossed [2 + 2]-cycloaddition. Due to the presence of the C-B bond, a variety of structures can be easily prepared that are not accessible by other methods. Moreover, a rare photo-ene reaction is also disclosed, allowing for the diastereoselective synthesis of trisubstituted borylated cyclopentanes.

Mercury (Hg) is a ubiquitous environmental contaminant known to bioaccumulate in biota and biomagnify in food webs. Parasites occur in nearly every ecosystem and often interact in complex ways with other stressors that their hosts experience. Hepatozoon spp. are intraerythrocytic parasites common in snakes. The Florida green watersnake (Nerodia floridana) and the banded watersnake (Nerodia fasciata) occur syntopically in certain aquatic habitats in the Southeastern United States. The purpose of this study was to investigate relationships among total mercury (THg) concentrations, body size, species, habitat type and prevalence and parasitemia of Hepatozoon spp. infections in snakes. In the present study, we sampled N. floridana and N. fasciata from former nuclear cooling reservoirs and isolated wetlands of the Savannah River Site in South Carolina. We used snake tail clips to quantify THg and collected blood samples for hemoparasite counts. Our results indicate a significant, positive relationship between THg and snake body size in N. floridana and N. fasciata in both habitats. Average THg was significantly higher for N. fasciata compared to N. floridana in bays (0.22 ± 0.02 and 0.08 ± 0.006 mg/kg, respectively; p < 0.01), but not in reservoirs (0.17 ± 0.02 and 0.17 ± 0.03 mg/kg, respectively; p = 0.29). Sex did not appear to be related to THg concentration or Hepatozoon spp. infections in either species. We found no association between Hg and Hepatozoon spp. prevalence or parasitemia; however, our results suggest that species and habitat type play a role in susceptibility to Hepatozoon spp. infection., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The saturation of aromatic scaffolds is valuable for the synthesis of complex rings. Herein, we demonstrate a process for photochemical dearomative reduction of quinolines. The process involves capture of a quinoline excited state with γ-terpinene. Importantly, the reaction is chemoselective as other easily reduced functionalities such as halogens or alkenes do not undergo reduction. The mechanism of the reaction has also been investigated. Finally, the generality of the approach towards other substrates is demonstrated.

Ophidiomycosis, also known as snake fungal disease, is caused by Ophidiomyces ophidiicola and is a threat to snake conservation worldwide. Ophidiomycosis has been reported throughout much of the eastern US, and outbreaks have been associated with local population declines of already strained populations. Previous studies report significant variability in ophidiomycosis among species sampled, with higher prevalence typically observed in Nerodia spp. Although ophidiomycosis can lead to morbidity and mortality in affected individuals, little is known about disease dynamics in free-ranging populations. Herein, we examine how individual-specific factors (e.g., life stage [immature, mature], contaminant status, sex, hemograms) may be associated with ophidiomycosis status in the brown watersnake (Nerodia taxispilota). During 2018-19, we sampled 97 N. taxispilota from five locations along the Savannah River in South Carolina and Georgia, US. Ophidiomyces ophidiicola DNA was detected in 66 snakes for a prevalence of 68% (95% confidence interval, 59-77). Mature snakes had a significantly higher risk of apparent ophidiomycosis (skin lesions present and quantitative PCR [qPCR], positive) relative to immature snakes. Snakes classified as having possible (skin lesions present, but qPCR negative) or apparent ophidiomycosis exhibited a relative azurophilia and heterophilia compared with individuals classified as negative (P≤0.037). Nerodia taxispilota in this region appear to have a high prevalence of apparent ophidiomycosis (22%; 95% CI, 14-31), similar to previous reports from the southeastern US. Additional epidemiologic investigations are warranted to further elucidate other individual-specific and environmental factors that may dictate disease risk and outcomes in affected populations., (© Wildlife Disease Association 2024.)

Alkene borylfunctionalization reactions have emerged as useful methods for chemical synthesis. While much progress has been made on 1,2-borylamination reactions, the related 1,1- and 1,3-borylaminations have not been reported. Herein, a Ni-catalyzed 1,1-borylamination of 1,1-disubstituted and monosubstituted alkenes and a 1,3-borylamination of cyclic alkenes are presented. Key to development of these reactions was the identification of an alkyllithium activator in combination with Mg salts. The utility of the products and the mechanistic details are discussed.

Rigid bicycles are becoming more popular in the pharmaceutical industry because they allow for expansion to new and unique chemical spaces. This work describes a new strategy to construct 2-azanorbornanes, which can act as rigid piperidine/pyrrolidine scaffolds with well-defined exit vectors. To achieve the synthesis of 2-azanorbornanes, new strain-release reagent, azahousane, is introduced along with its photosensitized strain-release formal cycloaddition with alkenes. Furthermore, new reactivity between a housane and an imine is disclosed. Both strategies lead to various substituted 2-azanorbornanes with good selectivities., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Objective: To explore the perspectives, barriers and enablers on salt reduction in out-of-home sectors in Malaysia among street food vendors, caterers and consumers., Design: A qualitative study involving twenty-two focus group discussions and six in-depth interviews was conducted, recorded and transcribed verbatim. An inductive thematic analysis approach was employed to analyse the data., Setting: Two in-depth interviews and twenty-two focus group discussions were conducted face-to-face. Four in-depth interviews were conducted online., Participants: Focus group discussions were conducted among twenty-three street food vendors, twenty-one caterers and seventy-six consumers of various eateries. In-depth interviews were conducted among two street food vendors and four caterers, individually., Results: Consumers and food operators perceived a high-salt intake within Malaysia's out-of-home food sectors. Food operators emphasised the necessity for a comprehensive salt reduction policy in the out-of-home sector involving all stakeholders. Consumers faced limited awareness and knowledge, counterproductive practices among food operators and challenges in accessing affordable low-Na food products, whereas food operators faced the lack of standardised guidelines and effective enforcement mechanisms and uncooperative consumer practices. Both groups expressed that food quality and price of salt were also the barriers, and they advocated for awareness promotion, enhanced regulation of manufactured food products and stricter enforcement targeting vendors. Consumers also suggested promoting and recognising health-conscious food premises, whereas food operators suggested on knowledge enhancement tailored to them, strategies for gaining consumers acceptance and maintaining food quality., Conclusions: These findings provide valuable insights that serve as foundational evidence for developing and implementing salt reduction policies within Malaysia's out-of-home sectors.

A strategy to achieve photosensitized [2 + 2] cycloadditions by means of temporary ring constraint is reported. Specifically, a dioxaborole is prepared that undergoes [2 + 2] cycloadditions with a wide variety of alkenes. This strategy overcomes some challenges with the cycloaddition of acyclic substrates. The products can be easily transformed into cyclobutyl diols or 1,4-dicarbonyl compounds; the latter represents a formal alkene vicinal diacylation. The synthetic utility of this method is shown in the synthesis of valuable heterocycles and biatriosporin D.

Objectives: The aim of this study was to assess the changes in salt intake and concomitant changes in blood pressure (BP) and cardiovascular disease (CVD) mortality in England from 2003 to 2018., Methods: National surveys and death registration data were used for the analysis of salt intake as measured by 24-h urinary sodium excretion (449-1069 participants per year), BP (2651-6738 participants per year) and CVD mortality., Results: A decline in salt intake from 9.38 (SD 4.64) to 7.58 (3.41) g/d was observed between 2003 and 2014 ( P  < 0.01), followed by an increase to 8.39 (4.13) g/d in 2018 ( P  < 0.01). Similar trends in BP and CVD mortality were also observed between 2003 and 2018. SBP/DBP decreased from 125.3 (15.92)/74.48 (11.33) mmHg to 122.57 (14.92)/73.33 (10.75) mmHg between 2003 and 2014 ( P  < 0.01), followed by a plateau up to 2018 [122.04 (14.64)/73.84 (10.54) mmHg, P  > 0.05]. Likewise, a fall in stroke and ischaemic heart disease mortality rates was observed between 2003 and 2014, from 12.24 and 43.44 cases per 100 000, to 8.19 and 27.23 cases per 100 000 ( P  < 0.01), respectively, followed by a plateau afterwards ( P  > 0.05)., Conclusion: The UK salt reduction programme was initially successful in reducing population salt intake by 19% (from 9.38 g/d in 2003 to 7.58 g/d in 2014). However, in recent years, the programme stalled and thus led to an interruption in the decline of salt intake. BP and CVD mortality reduction was also interrupted when salt reduction stalled. The changes in salt intake may have played an important role in the concomitant changes in BP and CVD mortality. Urgent action is needed to reinvigorate the UK's once world-leading salt reduction programme., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

A synthesis of (±)-phyltetralin is reported. Notable features of the synthesis include a diastereoselective Cu/Pd-catalyzed arylboration reaction and a Matteson homologation., Competing Interests: Conflict of Interest The authors declare no conflict of interest.

The synthesis and Cu/Pd-catalyzed arylboration of 1-silyl-1,3-cyclohexadiene is described. This diene is significant as it allows for synthesis of polyfunctional cyclohexane/enes. To achieve high levels of diastereoselectivity, the use of a pyridylidene Cu-complex was employed. In addition, through the use of a chiral catalyst, an enantioselective reaction was possible. Due to the presence of the silyl and boron substituents, the products can be easily diversified into a range of valuable cyclohexane/ene products., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

ConspectusCycloaddition reactions are an effective method to quickly build molecular complexity. As predicted by the Woodward-Hoffmann rules, concerted cycloadditions with alkenes allow for the constructions of all possible stereoisomers of product by use of either the Z or E geometry. While this feature of cycloadditions is widely used in, for example, [4 + 2] cycloadditions, translation to [2 + 2] cycloadditions is challenging because of the often stepwise and therefore stereoconvergent nature of these processes. Over the past decade, our lab has explored Lewis acid-promoted [2 + 2] cycloadditions of electron-deficient allenes or ketenes with alkenes. The concerted, asynchronous cycloadditions allow for the synthesis of various cyclobutanes with control of stereochemistry.Our lab developed the first examples of Lewis acid-promoted ketene-alkene [2 + 2] cycloadditions. Compared with traditional thermal conditions, Lewis acid-promoted conditions have several advantages, such as increased reactivity, increased yield, improved diastereoselectivity, and, for certain cases, inverse diastereoselectivity. Detailed mechanistic studies revealed that the diastereoselectivity was controlled by the size of the substituent and the barrier of a deconjugation event. However, these reactions required the use of stoichiometric amounts of EtAlCl 2 because of the product inhibition, which led us to investigate catalytic enantioselective [2 + 2] cycloadditions of allenoates with alkenes. Through the use of chiral oxazaborolidines, a broad range of cyclobutanes can be prepared with the control of enantioselectivity. Mechanistic experiments, including 2 D-labled alkenes and Hammett analysis, illuminate likely transition state models for the cycloadditions. Additional studies led to the development of Lewis acid-catalyzed intramolecular stereoselective [2 + 2] cycloadditions of chiral allenic ketones/esters with alkenes.The methods we developed have been instrumental in the synthesis of several families of natural products. Specifically, one key lactone motif in (±)-gracilioether F was constructed by a ketene-alkene [2 + 2] cycloaddition and subsequent regioselective Baeyer-Villiger oxidation sequence. Enantioselective allenoate-alkene [2 + 2] cycloadditions allowed for the synthesis of (-)-hebelophyllene E. Another attempt of applying this method in the synthesis of (+)-[5]-ladderanoic acid failed to deliver the desired cyclobutane because of an unexpected rearrangement. The key cyclobutane was later assembled by a stepwise carboboration/Zweifel olefination process. Finally, the stereoselective [2 + 2] cycloadditions of allenic ketones and alkenes was applied in the syntheses of (-)-[3]-ladderanol, (+)-hippolide J, and (-)-cajanusine.

The synthesis of polycyclic compounds is of high interest due to the prevalence of these motifs in drugs and natural products. Herein, we report on the stereoselective construction of 3D bicyclic scaffolds and azetidine derivatives by modulation of N-sulfonylimines to achieve either [4+2]- or [2+2]-cycloaddition reactions. The utility of the method was established by further modulation of the product. Mechanistic studies are also included, which support reaction via Dexter energy transfer., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Identification of rigid counterparts for common flexible scaffolds is crucial to the advancement of medicinal chemistry. Here we showcase a new class of building blocks, 2,5-disubstituted bicyclo[2.1.1]hexanes that can act as rigidified cis -, or trans -1,3-disubstituted cyclopentanes, common motifs in drugs. The scalable synthesis of these structures was enabled through the use of C-H functionalization logic and cycloaddition reactions., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Bismuth oxyhalides are a promising class of photocatalysts for harvesting solar energy. These materials are often synthesized in aqueous media with poor synthetic control resulting from the extremely fast nucleation and growth rates of the particles. These fast rates are caused by the rapid precipitation of bismuth salts with free halide ions. We have developed water-soluble precursors combining bismuth with either chlorine or bromine atoms in the same metal-organic complex. With the application of heat, halide ions are released, which then precipitate with bismuth ions as BiOX (X = Cl, Br). By controlling the halide ion formation rate, the nucleation and growth rates of BiOX materials can be tuned to provide synthetic control. The diverse potential of these precursors is demonstrated by synthesizing BiOX in three ways: aqueous colloidal synthesis, solid-state decomposition, and fabrication of films of BiOX via spray pyrolysis of the aqueous precursor solutions. These broadly applicable single-source precursors will enhance the ability to synthesize future BiOX materials with controlled morphologies.

Premise: Researchers often use ecological niche models to predict where species might establish and persist under future or novel climate conditions. However, these predictive methods assume species have stable niches across time and space. Furthermore, ignoring the time of occurrence data can obscure important information about species reproduction and ultimately fitness. Here, we assess compare ecological niche models generated from full-year averages to seasonal models., Methods: In this study, we generate full-year and monthly ecological niche models for Capsella bursa-pastoris in Europe and North America to see if we can detect changes in the seasonal niche of the species after long-distance dispersal., Results: We find full-year ecological niche models have low transferability across continents and there are continental differences in the climate conditions that influence the distribution of C. bursa-pastoris. Monthly models have greater predictive accuracy than full-year models in cooler seasons, but no monthly models can predict North American summer occurrences very well., Conclusions: The relative predictive ability of European monthly models compared to North American monthly models suggests a change in the seasonal timing between the native range to the non-native range. These results highlight the utility of ecological niche models at finer temporal scales in predicting species distributions and unmasking subtle patterns of evolution., (© 2023 The Authors. American Journal of Botany published by Wiley Periodicals LLC on behalf of Botanical Society of America.)

Background: High salt intake is a major cause of hypertension and cardiovascular diseases. The out-of-home sectors have been identified as one of the contributors of high salt intake in the population. The National Salt Reduction Policy of Malaysia was initiated in 2015; however, out-of-home sectors are yet to be emphasized and perception by policy-makers and the food industries towards salt reduction are yet unknown. This study aimed to determine the perceptions, barriers and enablers towards salt reduction in the out-of-home sector in Malaysia, as well as among policy-makers and the food industries., Methods: This is a qualitative study via semi-structured in-depth interviews (IDI) and focus group discussions (FGD) involving several stakeholders consisting of policy-makers from five ministries, five nongovernment organizations (NGOs) and food science/food technology researchers from five regions (West, North, East, and South Peninsular and East Malaysia/Borneo), as well as the food industries. The IDI and FGD sessions were recorded, transcribed verbatim and analysed thematically using Nvivo software version 12., Results: All participants agreed that salt intake in Malaysia is high and leads to hypertension and cardiovascular diseases. Lack of awareness, poor eating culture and behaviour and frequent eating out were among the causes of high salt intake. Awareness campaigns and education, sodium content labelling and product reformulation were strategies that have been implemented by the government; whilst for the food industries, some of them have tried to reduce salt and labelled the sodium content on their food products. However, there were several barriers including perceived poor consumer acceptance, lack of knowledge and resources, and challenges in reformulation, as well as unavailability of guidelines and salt targets. Hence, several enablers have been suggested, which include prioritizing the salt reduction strategy, creating more awareness, collaboration and engagement, research and technology particularly for reformulation and shelf-life stability, incentives and salt tax., Conclusions: Salt reduction efforts of the out-of-home sector in Malaysia could be achieved through several measures or enablers that can overcome the barriers currently faced by stakeholders, especially policy-makers, food industries and the consumers themselves. This study will benefit the policy-makers to improve the salt reduction policy of out-of-home sectors and highlight the concerns among the food industries on the policy., (© 2023. The Author(s).)

Two catalytic systems have been developed for the arylboration of endocyclic enecarbamates to deliver synthetically versatile borylated saturated N-heterocycles in good regio- and diastereoselectivities. A Cu/Pd dual catalytic reaction enables the synthesis of borylated, α-arylated azetidines, while a Ni-catalysed arylboration reaction efficiently functionalizes 5-, 6-, and 7-membered enecarbamates. In the case of the Cu/Pd-system, a remarkable additive effect was identified that allowed for broader scope. The products are synthetically useful, as demonstrated by manipulations of the boronic ester to access biologically active compounds., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Many humans live in large, complex political centers, composed of multi-scalar communities including neighborhoods and districts. Both today and in the past, neighborhoods form a fundamental part of cities and are defined by their spatial, architectural, and material elements. Neighborhoods existed in ancient centers of various scales, and multiple methods have been employed to identify ancient neighborhoods in archaeological contexts. However, the use of different methods for neighborhood identification within the same spatiotemporal setting results in challenges for comparisons within and between ancient societies. Here, we focus on using a single method-combining Average Nearest Neighbor (ANN) and Kernel Density (KD) analyses of household groups-to identify potential neighborhoods based on clusters of households at 23 ancient centers across the Maya Lowlands. While a one-size-fits all model does not work for neighborhood identification everywhere, the ANN/KD method provides quantifiable data on the clustering of ancient households, which can be linked to environmental zones and urban scale. We found that centers in river valleys exhibited greater household clustering compared to centers in upland and escarpment environments. Settlement patterns on flat plains were more dispersed, with little discrete spatial clustering of households. Furthermore, we categorized the ancient Maya centers into discrete urban scales, finding that larger centers had greater variation in household spacing compared to medium-sized and smaller centers. Many larger political centers possess heterogeneity in household clustering between their civic-ceremonial cores, immediate hinterlands, and far peripheries. Smaller centers exhibit greater household clustering compared to larger ones. This paper quantitatively assesses household clustering among nearly two dozen centers across the Maya Lowlands, linking environment and urban scale to settlement patterns. The findings are applicable to ancient societies and modern cities alike; understanding how humans form multi-scalar social groupings, such as neighborhoods, is fundamental to human experience and social organization., Competing Interests: The authors have declared that no competing interests exist.

A strategy for the photosensitized cycloaddition of alkenylboronates and allylic alcohols by a temporary coordination is presented. The process allows for the synthesis of a diverse range of cyclobutylboronates. Key to development of these reactions is the temporary coordination of the allylic alcohol to the Bpin unit. This not only allows for the reaction to proceed in an intramolecular manner but also allows for high levels of stereo and regiocontrol. A key aspect of these studies is the utility of the cycloadducts in the synthesis of complex natural products artochamin J and piperarborenine B.

The rapid buildup of molecular complexity from simple precursors is a key goal in organic chemistry. One strategy to achieve this is through a dearomative cycloaddition wherein a 2D arene and alkene is converted to a 3D structure. In many cases this type of reactivity has been achieved with photochemistry. Despite the prospect of such a reaction, most known variants are intramolecular, which greatly limits the scope of chemical space that can be accessed. Intermolecular variants are known but are generally limited to heterocyclic systems such as indoles or quinolines. Herein, a method for intermolecular dearomative cycloaddition of simple naphthalenes with alkenes is presented. The reactions operate by a photoinduced sensitization of the arene. The bridged bicyclic products are generated with control of regiochemistry and function for a range of alkenes. In addition, the products can serve as useful intermediates as demonstrated in the synthesis of a biologically active benzazapine analog. Mechanistic studies are also included, which support reaction via a triplet excited state and that the selectivity can be rationalized by spin-density calculations., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Aromatic ring isosteres and rigidified saturated hydrocarbons are important motifs to enable drug discovery. Herein we disclose [2]-ladderanes as a class of meta-substituted aromatic ring isosteres and rigidified cyclohexanes. A straightforward synthesis of the building blocks is presented along with representative derivatization. Preliminary studies reveal that the [2]-ladderanes offer similar metabolic and physicochemical properties thus establishing this class of molecules as interesting motifs., (© 2022. The Author(s).)

Cardiovascular behavioral medicine has significantly advanced the knowledge base regarding the mechanisms by which psychological and behavioral factors can impact cardiovascular function and has developed clear links between these factors and cardiovascular health and disease. More recent work has established numerous behavioral interventions that are efficacious, and in several cases demonstrated to be effective. However, despite these significant advances, translation to broad, real-world uptake and utilization has not been well studied, with consequential profound implications for health equity. The purpose of this article is to review what is known about effective implementation strategies to support the uptake of behavioral medicine interventions to improve cardiovascular health, to underscore the potential for developing additional implementation strategies for wide-scale uptake of effective cardiovascular behavioral medicine interventions, and to discuss the potential for developing additional implementation approaches while conducting early stage efficacy studies in this area. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Photochemical dearomative cycloaddition has emerged as a useful strategy to rapidly generate molecular complexity. Within this context, stereo- and regiocontrolled intermolecular para -cycloadditions are rare. Herein, a method to achieve photochemical cycloaddition of quinolines and alkenes is shown. Emphasis is placed on generating sterically congested products and reaction of highly substituted alkenes and allenes. In addition, the mechanistic details of the process are studied, which revealed a reversible radical addition and a selectivity-determining radical recombination. The regio- and stereochemical outcome of the reaction is also rationalized.

Cyclobutanes are important motifs that have found utility in many contexts. Prior work has demonstrated an enantioselective isomerization/stereoselective [2 + 2] as a means to access bicyclo [4.2.0] octanes. Herein, the utility of this method is demonstrated towards the synthesis of benzocyclobutenes and a key intermediate towards the endiandric acids., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and declare that GAM is the chair of Blood Pressure UK and Consensus Action on Salt, Sugar and Health (CASSH). FJH is a member of CASSH. Neither receive any financial support from these organisations.

A new strategy for the synthesis of highly versatile cyclobutylboronates via the photosensitized [2+2]-cycloaddition of alkenylboronates and alkenes is presented. The process is mechanistically different from other processes in that energy transfer occurs with the alkenylboronate as opposed to the other alkene. This strategy allows for the synthesis of an array of diverse cyclobutylboronates. The conversion of these adducts to other compounds as well as their utility in the synthesis of melicodenine C is demonstrated., (© 2022 Wiley-VCH GmbH.)

Saturated bicycles are becoming ever more important in the design and development of new pharmaceuticals. Here a new strategy for the synthesis of bicyclo[2.1.1]hexanes is described. These bicycles are significant because they have defined exit vectors, yet many substitution patterns are underexplored as building blocks. The process involves sensitization of a bicyclo[1.1.0]butane followed by cycloaddition with an alkene. The scope and mechanistic details of the method are discussed.

The crystal structures of three β-halolactic acids have been determined, namely, β-chlorolactic acid (systematic name: 3-chloro-2-hydroxypropanoic acid, C 3 H 5 ClO 3 ) (I), β-bromolactic acid (systematic name: 3-bromo-2-hydroxypropanoic acid, C 3 H 5 BrO 3 ) (II), and β-iodolactic acid (systematic name: 2-hydroxy-3-iodopropanoic acid, C 3 H 5 IO 3 ) (III). The number of molecules in the asymmetric unit of each crystal structure (Z') was found to be two for I and II, and one for III, making I and II isostructural and III unique. The difference between the molecules in the asymmetric units of I and II is due to the direction of the hydrogen bond of the alcohol group to a neighboring molecule. Molecular packing shows that each structure has alternating layers of intermolecular hydrogen bonding and halogen-halogen interactions. Hirshfeld surfaces and two-dimensional fingerprint plots were analyzed to further explore the intermolecular interactions of these structures. In I and II, energy minimization is achieved by lowering of the symmetry to adopt two independent molecular conformations in the asymmetric unit.