Planet-compatible pathways for transitioning the chemical industry.

Chemical products, such as plastics, solvents, and fertilizers, are essential for supporting modern lifestyles. Yet, producing, using, and disposing of chemicals creates adverse environmental impacts which threaten the industry's license to operate. This study presents seven planet-compatible pathways toward 2050 employing demand-side and supply-side interventions with cumulative total investment costs of US$1.2-3.7 trillion. Resource efficiency and circularity interventions reduce global chemicals demand by 23 to 33% and are critical for mitigating risks associated with using fossil feedstocks and carbon capture and sequestration, and constraints on available biogenic and recyclate feedstocks. Replacing fossil feedstocks with biogenic/air-capture sources, shifting carbon destinations from the atmosphere to ground, and electrifying/decarbonizing energy supply for production technologies could enable net negative emissions of 0.5 GtCO2eq y-1 across non-ammonia chemicals, while still delivering essential chemical-based services to society.

Global spatio-temporal change assessment in interregional water stress footprint in China by a high resolution MRIO model.

Developing effective strategies to alleviate increasing water stress in China requires an understanding of how consumption and production drive water stress footprints (WSF) at a high resolution and multiple spatial and temporal scales. However, current Chinese multi-regional input-output (CMRIO) models have limited resolution. Here, we build a high-resolution international MRIO model covering 31 Chinese provinces, 163 sectors, to address this issue, and then analyze the impact of changes in China's interprovincial and international trade patterns on the WSF from 2012 to 2017. We find that China's water stress embodied in inter-provincial trade has increased year after year, to 5606 km3 H2O-eq in 2017, exceeding 50 % of the total domestic footprint. Domestic water stress transfer is most apparent in the outsourcing of water stress from eastern coastal regions to Central and Western regions, with the top interregional supply chain paths mainly associated with the demand of processed rice and tobacco products. China has transformed into a net exporter of water stress in 2017, with water stress exports to developing countries accounting for 54 % of total exports, up from 51 % in 2012. With deepening globalization, trade between China and developing countries has boosted bilateral economic development, while also exacerbating water stress in China. In addition to agricultural cultivation, industrial products such as plastics and steel exported to meet international industries further contribute to water stress in Northern China. Further identify hotspots of water stress consumption is needed to prioritize actions to relieve regional water stress in a more effective manner, and our study can provide key information.

Complete Genomic Sequence of the Clinical Isolate Legionella pneumophila Serogroup 1 Strain 80-045 from Japan.

We report the complete genomic sequence of Legionella pneumophila serogroup 1 strain 80-045, isolated from autopsy lung tissue of the first patient diagnosed with Legionnaires' disease in Japan.

Preparation and Evaluation of a Powdered Rebamipide Mouthwash as In-Hospital Formulation: Considering Dispersion before Use in Patients.

In Japan, rebamipide (RB) mouthwash (RB-MW) for oral mucositis induced by cancer chemotherapy has been prepared using in-hospital formulation. Usually, RB-MW is prepared by dispersing crushed commercial RB tablets in the dispersion medium; however, uniformity is difficult to obtain due to low solubility. The current study aims is to prepare homogenously dispersed formulations using the fine particles of crushed tablets by a method that is convenient for hospital use. Commercial RB tablets were pre-milled at different milling times as "RB-Ts". A ground mixture was then prepared by co-grinding the RB-Ts with HPC-L or PVP K30 via a benchtop ball milling machine (MM400). The physicochemical properties of samples were evaluated for PXRD, FTIR, turbidity, particle size, and solubility. Although the milling of RB tablets decreased the crystallinity, the length of milling time did not affect them. In contrast, grinding using MM400 significantly decreased RB crystallinity; their PXRD patterns showed a halo, suggesting the amorphization of RB crystals by grinding. Although solubility and turbidity seemed to be affected by the type of polymer rather than the particle size, every ground mixture showed high dispersibility. Thus, grinding the RB-Ts with polymers appeared to be the most promising way to obtain stable dispersion as an in-hospital formulation.

Phosphoethanolamine Accumulation Protects Cancer Cells under Glutamine Starvation through Downregulation of PCYT2.

Tolerance to severe tumor microenvironments, including hypoxia and nutrient starvation, is a common feature of aggressive cancer cells and can be targeted. However, metabolic alterations that support cancer cells upon nutrient starvation are not well understood. Here, by comprehensive metabolome analyses, we show that glutamine deprivation leads to phosphoethanolamine (PEtn) accumulation in cancer cells via the downregulation of PEtn cytidylyltransferase (PCYT2), a rate-limiting enzyme of phosphatidylethanolamine biosynthesis. PEtn accumulation correlated with tumor growth under nutrient starvation. PCYT2 suppression was partially mediated by downregulation of the transcription factor ELF3. Furthermore, PCYT2 overexpression reduced PEtn levels and tumor growth. In addition, PEtn accumulation and PCYT2 downregulation in human breast tumors correlated with poor prognosis. Thus, we show that glutamine deprivation leads to tumor progression by regulating PE biosynthesis via the ELF3-PCYT2 axis. Furthermore, manipulating glutamine-responsive genes could be a therapeutic approach to limit cancer progression.

Effects of a Rebamipide Mouthwash on Stomatitis Caused by Cancer Chemotherapy-Evaluation of the Efficacy by Patients Themselves.

Anticancer drug-induced stomatitis develops in 30% to 40% of cancer cases that undergo chemotherapy. However, medications for this condition are not commercially available in Japan. Upon obtaining approval of the ethics committee, a mouthwash containing rebamipide as the active ingredient (rebamipide mouthwash) was administered to one inpatient and four outpatients, who had developed stomatitis caused by cancer chemotherapy. Starting from 14 d after the administration of the rebamipide mouthwash, the patients scored a stomatitis survey on oral state, pain level, and diet and recorded the number of times they gargled, as well as any stomatitis observations, in a stomatitis diary. The total scores for the points for each of the three types of survey sections were classified into Grades 0 to 4 and evaluated as a stomatitis evaluation score (SES). The SES became "0" in three out of the five patients within 14 d of treatment. No change in SES was found in one patient. In the remaining patients, SES became "0" once but increased again later. Using image analysis software (ImageJ), the area at which the stomatitis was observed was measured. When comparing SES and change in the area in patients who agreed to participate, gradual reductions in the extent of stomatitis was observed even during the period when SES did not change. Having patients fill in an observation chart was effective for grasping changes in symptoms in outpatients.

Congenital dermoid cyst at the anterior fontanelle: neuroimaging before and after fontanelle closure.

We report on a 2-month-old boy with a dermoid cyst arising at the anterior fontanelle, with observation during both the open and closed stages of the fontanelle. The etiology of this benign, curable tumor is discussed.

Design and pharmacological evaluation of PF-4840154, a non-electrophilic reference agonist of the TrpA1 channel.

TrpA1 is an ion channel involved in nociceptive and inflammatory pain. It is implicated in the detection of chemical irritants through covalent binding to a cysteine-rich intracellular region of the protein. While performing an HTS of the Pfizer chemical collection, a class of pyrimidines emerged as a non-reactive, non-covalently binding family of agonists of the rat and human TrpA1 channel. Given the issues identified with the reference agonist Mustard Oil (MO) in screening, a new, non-covalently binding agonist was optimized and proved to be a superior agent to MO for screening purposes. Compound 16a (PF-4840154) is a potent, selective agonist of the rat and human TrpA1 channel and elicited TrpA1-mediated nocifensive behaviour in mouse.

New iridoids from Gelsemium species.

Four new iridoids structurally related to gelsemide (5) were isolated from two Loganiaceous plants, Gelsemium elegans and G. rankinii. Among them, GEIR-1 (1) has a novel tetracyclic caged structure.

Elderberry bark lectins evolved to recognize Neu5Ac alpha2,6Gal/GalNAc sequence from a Gal/GalNAc binding lectin through the substitution of amino-acid residues critical for the binding to sialic acid.

Bark lectins from the elderberry plants belonging to the genus Sambucus specifically bind to Neu5Acalpha2,6Gal/GalNAc sequence and have long been used for the analysis of sialoglycoconjugates that play important roles in many biological phenomena. However, molecular basis of such a unique carbohydrate binding specificity has not been understood. To answer these questions, we tried to identify the amino-acid residues in the Japanese elderberry bark lectin, Sambucus sieboldiana agglutinin that enabled the lectin to recognize sialic acid by using in silico docking simulation and site-directed mutagenesis. These studies showed that three amino-acid residues, S(197), A(233) and Q(234), in the C-terminal subdomain of SSA-B chain are critical for the binding to the sialic acid in Neu5Acalpha2,6Gal/GalNAc sequence. Replacement of one of these residues to the one in the corresponding position of ricin B-chain completely abolished the binding to a sialoglycoprotein, fetuin. Conserved presence of these amino acid residues in the corresponding sequences of two other elderberry lectins with similar binding specificity further supported the conclusion. These findings indicated that the replacement of the corresponding amino-acid residues in a putative Gal/GalNAc-specific ancestral lectin to these amino-acid residues generated the unique Neu5Acalpha2,6Gal/GalNAc-specific elderberry lectins in the course of molecular evolution.

Four novel gelsenicine-related oxindole alkaloids from the leaves of Gelsemium elegans benth.

[reaction: see text] New types of four gelsenicine-related oxindole alkaloids were isolated from the leaves of Gelsemium elegans Benth. Gelsedilam (1) and 14-acetoxygelsedilam (2) are the first examples of 18,19-nor-type monoterpenoid indole alkaloids. Gelsefuranidine (3) and gelseiridone (4) have, respectively, an additional furan residue or an iridoid unit on the gelsenicine-related monoterpenoid indole alkaloid.