bluuebunny/crossref_metadata_2025 huggingface dataset:
Stones in Motion: monuments and chiefly title histories in central Vanuatu
Authors: Ballard Chris
Published: February 2023

This paper addresses the ways in which stones have anchored stories and people in central Vanuatu. Three different sets of stones, and stories about those stones, cast light from different angles on the history of the distinctive chiefly title system of this region. The first set revolves around the fulcrum of Wotanimanu, a pillar of stone that rises from the sea between Efate and the Shepherd Islands. This is the figure of a chief who arrived on Efate by sea, accompanied by his “stones” or people. Senior chiefly titles of this region, which draw on lengthy histories of migration, ground their narrative and genealogical claims in the proof of a second set of stones, including grave markers, magic stones, and arrangements of stones in series that stand for successive holders of each title. The third set of stones and stories was initiated by the first resident Presbyterian missionary in the Shepherd Islands, Oscar Michelsen, who acknowledged the importance attached locally to history by setting up a series of stelae to commemorate the conversion of individual chiefs. The paper concludes with thoughts on the agency and mobility of stone in the Shepherd Islands, and the ways in which stones give substance to chiefly power.
On the infrared coincidence: What is the jet contribution to the X‐ray power law in GX 339–4?
Authors: Russell David M.
Published: February 2023

The hard X‐ray power law, prominent in the hard state in black hole X‐ray binaries, is generally due to thermal Comptonization in the corona. Optically thin synchrotron emission from compact jets is commonly seen at infrared wavelengths in the hard state. The extent of this spectrum to higher energies remains uncertain. Here, a multi‐wavelength study of GX 339–4 is presented. The infrared (IR) to X‐ray spectral index is measured and compared to the X‐ray spectral index fitted separately. On some dates in which the jet dominates the IR emission, the X‐ray power law and the IR to X‐ray power‐law spectral indices are both in the range (where ), that is, photon index, . This suggests they could be the same power law with the same origin, or that this is a coincidence. On other dates in the hard state, , ruling out a common origin. It is likely that Comptonization dominates on most dates, as expected. However, the X‐ray power law never appears to be fainter than the jet power law extrapolated from IR to X‐ray, implying that the jet contribution imposes a lower limit to the X‐ray flux. If confirmed, this would imply the cooling break in the synchrotron spectrum probably resides at X‐ray or higher energies. It is suggested that X‐ray spectral fitting should include an extra power law with a break (ideally fit to IR too).
Ornamental cabbage (Brassica oleracea var. acephala) responses to phytase enzyme purified from Lactobacillus coryniformis application
Authors: Dikbaş Neslihan , Parlakova Karagöz Fazilet , Uçar Sevda , Demir Yeliz
Published: February 2023

In order to increase the quality and yield of ornamental plants, especially potted ornamental plants, it is necessary to enrich the physical properties of the growing medium and to ensure the continuity of the growing medium. In order to achieve this, organic substances that create a serious cost in ornamental plant cultivation are added to the growing medium. This study was planned to assess the role of inoculation of different levels in the seeds and soaking times of purified phytase, on the plant growth and ornamental plant decorative values in ornamental cabbage plants under nutrient limiting condition in greenhouse. Different doses (E0: 0 EU, E1: 5 EU, E2: 10 EU), soaking times (W15: 15 min, W30: 30 min, W60: 60 min), and their combinations (W15 + E0, W15 + E1, W15 + E2, W30 + E0, W30 + E1, W30 + E2, W60 + E0, W60 + E1, W60 + E2) of phytase enzyme purified and isolated from the Lactobacillus coryniformis were applied to ornamental cabbage seeds, and they were sown in plug trays filled with appropriate growing medium. Seedlings were planted in plastic pots during their period when the seedlings had four to five true leaves. Treatments of phytase enzyme purified and isolated from the microorganism generally improved the observed parameters. The application of, especially, the highest level of phytase enzyme doses increased the plant height, main stem height, and stem diameter of ornamental cabbage as compared to control (E0 treatment: distilled water). While the highest number of leaves per plant was obtained at E1 and E2 application doses and W30 and W60 soaking times; the highest stem diameter was obtained at E2 application doses and W30 and W60 soaking times. The present study clarified that the purified phytase enzyme can increase ornamental cabbage quality at the appropriate concentration and soaking time and is a promising biotechnology material for agricultural applications, and especially in different ornamental plant species.
Bestimmung der Scherfestigkeit und Steifigkeit von Gel‐Sand‐Injektionsprobekörpern
Authors: Trunk Ulrich , Braun Julian , Rüdlin Christian , Pandrea Paul
Published: February 2023

Injektionen von Sanden und sandreichen Kiesen mit mineralischen Bindemitteln sind mit besonderen Herausforderungen verbunden, auch Feinstzemente können nur für spezielle Aufgaben verwendet werden. So erfahren die Injektionen mit Gelen – Acrylatgele und umweltverträgliche Gele auf Natriumsilikatbasis – mittlerweile eine erhöhte Aufmerksamkeit. An der Universität der Bundeswehr München (UniBW) wurde die Erhöhung der Scherfestigkeit von Sanden durch Injektionen mit Acrylatgel‐Sandproben durch Laborversuche untersucht. An mit einem Weichgel auf Natriumsilikatbasis (Neutrogel) injizierten Sandproben konnte in ersten Versuchsreihen an der Fachhochschule Nordwestschweiz, FHNW, ebenfalls eine deutliche Erhöhung der Scherfestigkeit ermittelt werden. Dies war Anlass, umfangreichere Versuchsserien zur Bestimmung der Scherfestigkeit von Acrylatgel‐Sandproben – mit Acrylatgelen verschiedener Hersteller – und Neutrogel‐Sandproben durchzuführen. Ausgeführt wurden neben einaxialen Druckversuchen und direkten Scherversuchen vorwiegend Triaxialversuche. Mit den Versuchen stehen erstmals Vergleichswerte der Scherfestigkeiten und Steifigkeiten unterschiedlicher Gel‐Sand‐Mischungen zur Verfügung. Die durch die Gele induzierte Kohäsion führt zu bautechnisch signifikanten Erhöhungen der Scherfestigkeit der Gel‐Sandproben.
N2‐fixation can sustain wastewater treatment performance of photogranules under nitrogen‐limiting conditions
Authors: Trebuch Lukas M. , Schoofs Kobe , Vaessen Stijn M. F. , Neu Thomas R. , Janssen Marcel , Wijffels René H. , Vet Louise E. M. , Fernandes Tânia V.
Published: February 2023

Wastewater characteristics can vary significantly, and in some municipal wastewaters the N:P ratio is as low as 5 resulting in nitrogen‐limiting conditions. In this study, the microbial community, function, and morphology of photogranules under nitrogen‐replete (N+) and limiting (N−) conditions was assessed in sequencing batch reactors. Photogranules under N− condition were nitrogen deprived 2/3 of a batch cycle duration. Surprisingly, this nitrogen limitation had no adverse effect on biomass productivity. Moreover, phosphorus and chemical oxygen demand removal were similar to their removal under N+ conditions. Although performance was similar, the difference in granule morphology was obvious. While N+ photogranules were dense and structurally confined, N− photogranules showed loose structures with occasional voids. Microbial community analysis revealed high abundance of cyanobacteria capable of N2‐fixation. These were higher at N− (38%) than N+ (29%) treatments, showing that photogranules could adjust and maintain treatment performance and high biomass productivity by means of N2‐fixation.
Overexpression of the sulfate transporter‐encoding SULTR2 increases chromium accumulation in Chlamydomonas reinhardtii
Authors: Tang Yuxin , Zhang Baolong , Li Zhaoyang , Deng Ping , Deng Xuan , Long Huan , Wang Xun , Huang Kaiyao
Published: February 2023

Hexavalent chromium [Cr(Ⅵ)] is a highly toxic contaminant in aquatic systems, and microalgae represent promising bioremediators of metal‐containing wastewater. However, the metal‐binding capacity of algal cells is limited. Therefore, we improved the cellular Cr(Ⅵ) biosorption capacity of Chlamydomonas reinhardtii by overexpressing the sulfate transporter gene SULTR2. SULTR2 was predominantly located in the cytoplasm of the cell, and few proteins mobilized to the cell membrane as a Cr transporter under Cr stress conditions. Intracellular Cr accumulation was almost doubled in SULTR2‐overexpressing transgenic strains after exposure to 30 μM K2Cr2O7 for 4 d. Alginate‐based immobilization increased the rate of Cr removal from 43.81% to 88.15% for SULTR2‐overexpressing transgenic strains after exposure to 10 μM K2Cr2O7 for 6 d. The immobilized cells also displayed a significant increase in nutrient removal efficiency compared to that of free‐swimming cells. Therefore, SULTR2 overexpression in algae has a great potential for the bioremediation of Cr(Ⅵ)‐containing wastewater.
Process intensification strategies toward cell culture‐based high‐yield production of a fusogenic oncolytic virus
Authors: Göbel Sven , Jaén Karim E. , Dorn Marie , Neumeyer Victoria , Jordan Ingo , Sandig Volker , Reichl Udo , Altomonte Jennifer , Genzel Yvonne
Published: February 2023

We present a proof‐of‐concept study for production of a recombinant vesicular stomatitis virus (rVSV)‐based fusogenic oncolytic virus (OV), rVSV‐Newcastle disease virus (NDV), at high cell densities (HCD). Based on comprehensive experiments in 1 L stirred tank reactors (STRs) in batch mode, first optimization studies at HCD were carried out in semi‐perfusion in small‐scale cultivations using shake flasks. Further, a perfusion process was established using an acoustic settler for cell retention. Growth, production yields, and process‐related impurities were evaluated for three candidate cell lines (AGE1.CR, BHK‐21, HEK293SF)infected at densities ranging from 15 to 30 × 106 cells/mL. The acoustic settler allowed continuous harvesting of rVSV‐NDV with high cell retention efficiencies (above 97%) and infectious virus titers (up to 2.4 × 109 TCID50/mL), more than 4–100 times higher than for optimized batch processes. No decrease in cell‐specific virus yield (CSVY) was observed at HCD, regardless of the cell substrate. Taking into account the accumulated number of virions both from the harvest and bioreactor, a 15–30 fold increased volumetric virus productivity for AGE1.CR and HEK293SF was obtained compared to batch processes performed at the same scale. In contrast to all previous findings, formation of syncytia was observed at HCD for the suspension cells BHK 21 and HEK293SF. Oncolytic potency was not affected compared to production in batch mode. Overall, our study describes promising options for the establishment of perfusion processes for efficient large‐scale manufacturing of fusogenic rVSV‐NDV at HCD for all three candidate cell lines.
Evaluation of the stability of polyamines in human serum at different storage temperatures using capillary electrophoresis with indirect ultraviolet detection
Authors: da Silva Ana Paula , Nishida Sônia , Calixto Leandro Augusto , da Silva Heron Dominguez Torres , Moraes Maria Lourdes Leite
Published: February 2023

Polyamines are low molecular weight compounds that are present in all living organisms. They are related to the pathological processes, and have been studied as biomarkers for tumor progression, being analyzed in patients’ biological fluids. However, polyamines can undergo degradation in serum samples, depending on storage conditions, which impairs their quantification in these matrices. In this work, capillary electrophoresis using indirect ultraviolet detection has been developed and applied to evaluate the stability of polyamines [cadaverine (Cad), putrescine (Put), spermine (Spm), and spermidine (Spd)] in human serum at different storage temperatures. By using this method, Cad, Put, Spm, and Spd were separated in less than 4 min. The range of the correlation coefficients was 0.993–0.998. The corresponding limits of detection and quantification were as follows (in mg L–1): Spm: 0.209 and 0.697; Spd: 0.165 and 0.549; Put: 0.189 and 0.632; Cad: 0.125 and 0.417. Besides, the coefficient of variation was lower than 1% for all analytes and the recovery was 92%–110%. The method was successfully applied for polyamines spiked in human serum samples from healthy people. The results showed that the degradation of polyamines was lower in samples stored in a freezer (−20°C).
Human plasma ricinine quantification by LC–HRMS after micro‐solid‐phase elution
Authors: Thiebot Pauline , Maaziz Nada , Oppon Chrystelle , Bertolo Laetitia , Magny Romain , Chevillard Lucie , Mégarbane Bruno , Houzé Pascal , Labat Laurence
Published: February 2023

A rapid, sensitive and specific method for ricinine identification and quantification in plasma has been developed by LC–HRMS. Deuterated ricinine was used as the internal standard. From 100 μL of plasma, ricinine was extracted using micro‐solid‐phase elution, which allows a reduced extraction time, by eliminating the evaporation step. Eluate is directly injected into the LC–HRMS system. Chromatographic separation was performed using a reverse‐phase C18 column with a 4.5 min gradient elution. The method was validated according to European Medicines Agency guidelines. Linearity was verified between 0.25 and 500.0 ng/mL; the maximum precision calculated was 19.9% for the lower limit of quantitation and 9.6% for quality control, and accuracy was within ± 5.6% of the nominal concentrations. Selectivity, carryover, matrix effect and stability were also verified according to European Medicines Agency guidelines. The method allows the rapid and reliable identification of ricin‐exposed victims in case of terrorist attacks or poisonings: three intoxication cases are reported.
Depth filter material process interaction in the harvest of mammalian cells
Authors: Parau Maria , Pullen James , Bracewell Daniel G.
Published: February 2023

Upstream advances have led to increased mAb titers above 5 g/L in 14‐day fed‐batch cultures. This is accompanied by higher cell densities and process‐related impurities such as DNA and Host Cell Protein (HCP), which have caused challenges for downstream operations. Depth filtration remains a popular choice for harvesting CHO cell culture, and there is interest in utilizing these to remove process‐related impurities at the harvest stage. Operation of the harvest stage has also been shown to affect the performance of the Protein A chromatography step. In addition, manufacturers are looking to move away from natural materials such as cellulose and Diatomaceous Earth (DE) for better filter consistency and security of supply. Therefore, there is an increased need for further understanding and knowledge of depth filtration. This study investigates the effect of depth filter material and loading on the Protein A resin lifetime with an industrially relevant high cell density feed material (40 million cells/ml). It focuses on the retention of process‐related impurities such as DNA and HCP through breakthrough studies and a novel confocal microscopy method for imaging foulant in‐situ. An increase in loading of the primary‐synthetic filter by a third, led to earlier DNA breakthrough in the secondary filter, with DNA concentration at a throughput of 50 L/m2 being more than double. Confocal imaging of the depth filters showed that the foulant was pushed forward into the filter structure with higher loading. The additional two layers in the primary‐synthetic filter led to better pressure profiles in both primary and secondary filters but did not help to retain HCP or DNA. Reduced filtrate clarity, as measured by OD600, was 1.6 fold lower in the final filtrate where a synthetic filter train was used. This was also associated with precipitation in the Protein A column feed. Confocal imaging of resin after 100 cycles showed that DNA build‐up around the outside of the bead was associated with synthetic filter trains, leading to potential mass transfer problems.
Hypoxia‐induced oxidative stress promotes therapy resistance via upregulation of heme oxygenase‐1 in multiple myeloma
Authors: Abe Ko , Ikeda Sho , Nara Miho , Kitadate Akihiro , Tagawa Hiroyuki , Takahashi Naoto
Published: February 2023

Background

Multiple myeloma (MM) is a hematopoietic malignancy for which proteasome inhibitors have become available in recent years. However, many patients develop resistance to these drugs during treatment. Therefore, it is important to elucidate the mechanisms underlying resistance acquisition by proteasome inhibitors. Side population (SP) cells, which have a high drug efflux capacity and hypoxic responses in the microenvironment have both provided important insights into drug resistance in MM; however, little is known about the characteristics of SP cells in hypoxic microenvironments.

Methods

We performed cDNA microarray analysis for SP and non‐SP obtained from RPMI‐8226 and KMS‐11 cell lines cultured for 48 h in normoxic and hypoxic conditions (1% O2). Genes specifically upregulated in hypoxic SP were examined.

Results

Our comprehensive gene expression analysis identified HMOX1, BACH2, and DUX4 as protein‐coding genes that are specifically highly expressed in SP cells under hypoxic conditions. We have shown that HMOX1/heme oxygenase‐1 (HMOX1/HO‐1) is induced by hypoxia‐inducible reactive oxygen species (ROS) and reduces ROS levels. Furthermore, we found that HMOX1 contributes to hypoxia‐induced resistance to proteasome inhibitors in vitro and in vivo. Excessive ROS levels synergistically enhance bortezomib sensitivity. In clinical datasets, HMOX1 had a strong and significantly positive correlation with MAFB but not MAF. Interestingly, hypoxic stimulation increased MAFB/MafB expression in myeloma cells; in addition, the knockdown of MAFB under hypoxic conditions suppressed HMOX1 expression.

Conclusion

These results suggest that the hypoxia‐ROS‐HMOX1 axis and hypoxia‐induced MafB may be important mechanisms of proteasome inhibitor resistance in hypoxic microenvironments.
No association of malignant B‐cell non‐Hodgkin lymphomas with ipsilateral SARS‐CoV‐2 vaccination
Authors: Claaß Luise Victoria , Mayr Patrick , Paschold Lisa , Weber Thomas , Terziev Denis , Jehs Bertram , Brill Richard , Dober Johannes , Märkl Bruno , Wickenhauser Claudia , Czapiewski Piotr , Trepel Martin , Claus Rainer , Binder Mascha
Published: February 2023

Purpose

SARS‐CoV‐2 vaccines cause acute ipsilateral lymph node swelling in an important proportion of vaccines. Thus far, no malignant lymphadenopathies have been reported in temporal context to vaccination in the ipsilateral draining lymph node areas.

Experimental design

Prompted by two cases with unilateral axillary lymphomas that occurred ipsilaterally to prior SARS‐CoV‐2 vaccination, we systematically retrieved all B‐cell non‐Hodgkin lymphomas at two German University Medical Centers diagnosed before and after introduction of SARS‐CoV‐2 vaccines in Germany. Available lymphoma tissue (n=19) was subjected to next‐generation immunosequencing of the IGH locus. Malignant clonotypes were mined in the CoVabDab database and published data sets from 342 uninfected individuals, 55 individuals 28 days after anti‐SARS‐CoV‐2 vaccination and 139 individuals with acute COVID‐19 together encompassing over 1 million CDR3 sequences in total.

Results

Of 313 newly diagnosed cases in the two centers and observation periods, 27 unilateral manifestations in the defined deltoid draining regions were identified. The majority thereof were diffuse large B‐cell lymphomas (18 of 27 cases). Eleven unilateral cases were diagnosed in the era of SARS‐CoV‐2 vaccination and 16 in the control period before introduction of such vaccines. Of the 11 unilateral lymphomas that occurred during the vaccination period, ten had received a SARS‐CoV‐2 vaccine prior to lymphoma diagnosis. These cases were further evaluated. While left‐sided were more frequent than right‐sided lymphomas (19 vs 8 cases), no statistically significant association of vaccination site and laterality of the lymphoma manifestation was found. The unilateral lymphomas showed a normal range of B‐cell receptors typically found in these lymphoma subtypes with no evidence for anti‐SARS‐CoV‐2 sequences in the malignant clonotype.

Conclusions

Together, we found no evidence that the current SARS‐CoV‐2 vaccines could serve as a trigger for lymphomagenesis in the draining lymph node areas of the deltoid region used for vaccination.
Deacetylation of Arabinofuranosylated Xylopyranosyl Residues Related to Plant Xylan: Significant Differences Between Xylan Deacetylases Classified into Various Carbohydrate Esterase Families
Authors: Bella Maroš , Poláková Monika , Puchart Vladimír
Published: February 2023

A chemical synthesis of two novel phenyl glycosides of trisaccharides related to acetylarabinoxylan is described. The trisaccharides bear acetyl and arabinofuranosyl moieties at the non‐reducing‐end xylopyranosyl residue, which is substituted at positions 2 and 3. Both compounds were treated with various xylan deacetylases classified in different carbohydrate esterase (CE) families and significant differences between the families were found. While the arabinosylation hampers deacetylation by CE2‐CE5 and CE12 family members, both epitopes are deesterified by CE1 and in particular CE6 enzymes. The 3‐O‐acetylated 2‐O‐arabinosylated compound is also processed by CE7 and majority of CE16 esterases, but not by a hitherto non‐classified Flavobacterium johnsoniae acetylxylan esterase. The data suggests that a slow deesterification of the 2‐O‐acetylated 3‐O‐arabinosylated compound may be due to the acetyl group migration followed by deacetylation of this migration product.
Severe length‐dependent peripheral polyneuropathy in a patient with subacute combined spinal cord degeneration secondary to recreational nitrous oxide abuse: A case report and literature review
Authors: Bonev Ventzislav , Wyatt Mark , Barton Matthew J. , Leitch Michael A.
Published: February 2023

Nitrous oxide abuse can have detrimental effects on the central and peripheral nervous systems. This case study report aims to demonstrate a combination of severe generalized sensorimotor polyneuropathy and cervical myelopathy related to vitamin B12 deficiency following nitrous oxide abuse. We present a clinical case study and literature review examining primary research—published between 2012 and 2022—reporting nitrous oxide abuse affecting the spinal cord (myelopathy) and peripheral nerves (polyneuropathy); 35 articles were included in the review with a total of 96 patients, where the mean “patients” age was 23.9 years and were in a 2:1 male/female ratio. Of the 96 cases, within the review, 56% of patients were diagnosed with polyneuropathy, most commonly impacting the nerves of the lower limb (62%), while 70% of patients were diagnosed with myelopathy, most commonly impacting the cervical region (78%) on the spinal cord. In our clinical case study, a 28‐year‐old male underwent a multitude of diagnostic investigations for bilateral “foot drop” and sense of lower limb stiffness as ongoing complications of a vitamin B12 deficiency secondary to recreational nitrous oxide abuse. Both the literature review and our case report emphasize the dangers of recreational nitrous oxide inhalation, colloquially termed “nanging” and the risks it presents to both the central and peripheral nervous systems, which is erroneously considered by many recreational drug users to be less harmful than other illicit substances.
Superficial temporal artery access for carotid artery stenting: A case report
Authors: Csavajda Ádám , Nardai Sándor , Bertrand Olivier F. , Ruzsa Zoltán
Published: February 2023

Percutaneous intervention of patients who suffer from generalized vascular disease is often a great challenge due to the limited accessibility of the access gates. We discuss the case of a 66‐year‐old man who presented with critical right internal carotid artery (ICA) stenosis after previous hospitalization due to stroke. In addition to arteria lusoria, the patient had known bilateral femoral amputation, occlusion of the left ICA and significant three‐vessel coronary artery disease. After unsuccessful common carotid artery (CCA) cannulation from the right distal radial artery access, we successfully performed the diagnostic angiography and the planned right ICA‐CCA intervention using superficial temporal artery (STA) puncture. We showed that STA access can be used as an alternative and additional access site for diagnostic carotid artery angiography and intervention when standard access sites alone are insufficient.
Pt : Ge Ratio as a Lever of Activity and Selectivity Control of Supported PtGe Clusters in Thermal Dehydrogenation**
Authors: Poths Patricia , Zandkarimi Borna , Alexandrova Anastassia N. , Jimenez‐Izal Elisa
Published: February 2023

Ethylene is a key molecule in the chemical industry and it can be obtained through the catalytic dehydrogenation of ethane. Pt‐based catalysts show high performance toward alkane dehydrogenation, but suffer from coke formation and sintering that deactivate the catalyst. Ge was recently discovered to be a promising alloying element that suppresses deactivation of Pt while preserving its catalytic activity toward alkane dehydrogenation. This work explores the effect of the Ge content in supported PtGe cluster alloys, on the activity toward ethane dehydrogenation, selectivity against deeper dehydrogenation and coking, and sintering resistance. The model proposed herein is a tetrameric Pt cluster supported on magnesia, with varying amounts of added Ge. The phase diagram for these clusters was computed using global optimization at the density functional theory level, and under the paradigm of a statistical ensemble of many states populated by clusters at catalytic temperatures. The phase diagram shows that various Ge contents should be synthetically accessible, with Pt4Ge/MgO and Pt4Ge4/MgO being the most likely phases. The subsequent adsorption and mechanistic studies show that the clusters with the 1 : 4 Ge to Pt ratio (Pt4Ge/MgO) feature the largest resistance to sintering and best selectivity in the ethane dehydrogenation toward ethylene. Clusters without Ge are too active and easily coke, whereas clusters with higher Ge content start losing the catalytic activity toward ethane dehydrogenation. Thus, Ge concentration is a lever of control of Pt cluster stability and selectivity, and of cluster catalyst design. The effect of the Ge concentration on the cluster properties is explained on the basis of the electronic structure.
Drop Size Distributions as a Function of Dispersed Phase Viscosity: Experiments and Modeling
Authors: Hohl Lena , Röhl Susanne , Kraume Matthias
Published: February 2023

Detailed measurements of dynamic and steady‐state drop size distributions were performed in liquid‐liquid systems with water and different silicone oils using an in situ endoscope technique in a discontinuously operated stirred tank. The oils used as the dispersed phase vary in dynamic viscosity, while density and interfacial tension are nearly constant. The performance of a population balance model for partially mobile interfaces and its ability to predict steady‐state and dynamic Sauter mean diameters and the complete drop size distributions as a function of dispersed phase viscosity and different process parameters are evaluated. Furthermore, the impact of different daughter drop size distribution shapes on simulation results is quantified.
Fluorescence Detection of the Persistent Organic Pollutant Chlordecone in Water at Environmental Concentrations
Authors: Della‐Negra Oriane , Kouassi Aya Esther , Dutasta Jean‐Pierre , Saaidi Pierre‐Loïc , Martinez Alexandre
Published: February 2023

Chlordecone (CLD), a Persistent Organic Pollutant, is still present in water and food chain of the French West Indies (FWI), leading to dramatical public health problems. One of the major issues is the lack of an easy, non‐expensive, sensitive and robust method for the detection of chlordecone to ensure chlordecone‐free water and foods for the residents of the FWI. This study reports on the development of a fluorescent molecular cage that allows a simple and convenient detection of chlordecone in water at environmental concentration. The specific structural features of chlordecone prompted the choice of hemicryptophanes as receptor. First, the size, shape of the cavity, as well as the recognition units, were optimized to identify the most efficient non fluorescent host for CLD complexation. Then, this selected compound was equipped with fluorophores at different positions in order to find the most efficient system for CLD detection by fluorescence. Among the two most promising fluorescent cages, the newly synthesized hemicryptophane with biphenyl moieties allowed the development of a fast, easy, reproducible and cheap procedure to detect CLD in water. Based on its sensitivity and scalability, with modulation of hemicryptophane, concentration, CLD concentrations were estimated over five orders of magnitude (10−2–103 μg/L) including the environmental levels of contamination and the permissible limit for drinking water in the FWI.
Double Addition vs. Ring Closure: Systematic Reactivity Study of CO(NCO)2 and CO(NCS)2 towards Hydrogen Halides
Authors: Pfeiffer Jonathan , Günther Hennes , Völlinger Lena , Botros Demian , Scheibe Benjamin , Möbs Martin , Kraus Florian , Weigend Florian , Tambornino Frank
Published: February 2023

The reactivity of carbonyl diisocyanate, CO(NCO)2, and carbonyl diisothiocyanate, CO(NCS)2 with nucleophiles shows different patterns: Whereas carbonyl diisocyanate adds two equivalents of nucleophile forming carbonyl bis(carbamoylhalides), carbonyl diisothiocyanate only adds one equivalent and undergoes intramolecular ring closure, resulting in the formation of substituted thiadiazines. In this study we have reacted both carbonyl diisocyanate and carbonyl diisothiocyanate with the full series of hydrogen halides HF to HI, isolating carbonyl bis(carbamoylfluoride) (1), ‐chloride (2), ‐bromide (3), and ‐iodide (4) as well as (6‐chloro‐2,3‐dihydro‐2‐thioxo‐4H‐1,3,5‐thiadiazin‐4‐one (5), and 6‐bromo‐2,3‐dihydro‐2‐thioxo‐4H‐1,3,5‐thiadiazin‐4‐one (6). The compounds were analysed by single‐crystal X‐ray diffraction, NMR spectroscopy, IR and Raman spectroscopy, and elemental analysis. Quantum mechanical calculations show thermodynamic reasons for the differences in reactivity.
The Boekelheide Rearrangement of Pyrimidine N‐oxides as a Case Study of Closed or Open Shell Reactions ‐ Experimental and Computational Evidence for the Participation of Radical Intermediates
Authors: Kurzawa Timon , Zimmer Reinhold , Würthwein Ernst‐Ulrich , Reissig Hans‐Ulrich
Published: February 2023

In a case study, the acetic anhydride‐promoted reaction of a model pyrimidine N‐oxide to the corresponding 4‐acetoxymethyl‐substituted pyrimidine derivative (Boekelheide rearrangement) was investigated in detail by experiment and quantum chemical calculations. The reaction conditions were varied and several side products formed in low to moderate yields were identified. These experiments indicate that a (pyrimidin‐4‐yl)methyl radical is one of the key species of the rearrangement. This interpretation was supported by the fact that rearrangements performed in solvents which can easily lose hydrogen atoms, afford considerable quantities of products incorporating the solvent. With TEMPO the key radical could be trapped. Other carboxylic acid anhydrides confirm the conclusion that the Boekelheide rearrangement of the model pyrimidine N‐oxide proceeds, at least in part, via radical intermediates. The high level closed and open shell quantum chemical calculations show that concerted [3,3]‐sigmatropic rearrangements or stepwise processes, either via ion pairs or via radicals, are energetically feasible.
White Light‐Emitting Electrochemical Cells Employing Phosphor‐Sensitized Thermally Activated Delayed Fluorescence to Approach All‐Phosphorescent Device Efficiencies
Authors: Chen Xuan‐Jun , Huang Yu‐Ting , Luo Dian , Chang Chih‐Hao , Lu Chin‐Wei , Su Hai‐Ching
Published: February 2023

Solid‐state light‐emitting electrochemical cells (LECs) show promising advantages of simple device architecture, low operation voltage, and insensitivity to the electrode work functions such that they have high potential in low‐cost display and lighting applications. In this work, novel white LECs based on phosphor‐sensitized thermally activated delayed fluorescence (TADF) are proposed. The emissive layer of these white LECs is composed of a blue‐green phosphorescent host doped with a deep‐red TADF guest. Efficient singlet‐to‐triplet intersystem crossing (ISC) on the phosphorescent host and the subsequent Förster energy transfer from the host triplet excitons to guest singlet excitons can make use of both singlet and triplet excitons on the host. With the good spectral overlap between the host emission and the guest absorption, 0.075 wt.% guest doping is sufficient to cause substantial energy transfer efficiency (ca. 40 %). In addition, such a low guest concentration also reduces the self‐quenching effect and a high photoluminescence quantum yield of up to 84 % ensures high device efficiency. The phosphor‐sensitized TADF white LECs indeed show a high external quantum efficiency of 9.6 %, which is comparable with all‐phosphorescent white LECs. By employing diffusive substrates to extract the light trapped in the substrate, the device efficiency can be further improved by ca. 50 %. In the meantime, the intrinsic EL spectrum and device lifetime of the white LECs recover since the microcavity effect is destroyed. This work successfully demonstrates that the phosphor‐sensitized TADF white LECs are potential candidates for efficient white light‐emitting devices.
Ruthenium‐Catalyzed Cycloaddition for Introducing Chemical Diversity in Second‐Generation β‐Lactamase Inhibitors
Authors: Bouchet Flavie , Barnier Jean‐Philippe , Sayah Ines , Bagdad Youcef , Miteva Maria A. , Arthur Michel , Ethève‐Quelquejeu Mélanie , Iannazzo Laura
Published: February 2023

Ruthenium(II) alkyne azide cycloaddition (RuAAC) is an attractive reaction to access 1,5‐triazole derivatives and is applicable to internal alkynes. Here, we explore RuAAC to introduce molecular diversity on the diazabicyclooctane (DBO) scaffold of β‐lactamase inhibitors. The methodology presented is fully regioselective and enabled synthesis of a series of 1,5‐triazole DBOs and trisubstituted analogues. Molecular modelling and biological evaluation revealed that the DBO substituents provided putative stabilizing interactions in the active site of broad‐spectrum β‐lactamase KPC‐2 and promising activity against a hyperpermeable strain of Escherichia coli producing KPC‐2.
A Computational Workflow for Analysis of 3′ Tag‐Seq Data
Authors: Paropkari Akshay D. , Bapat Priyanka S. , Sindi Suzanne S. , Nobile Clarissa J.
Published: February 2023

RNA‐sequencing (RNA‐seq) is a gold‐standard method to profile genome‐wide changes in gene expression. RNA‐seq uses high‐throughput sequencing technology to quantify the amount of RNA in a biological sample. With the increasing popularity of RNA‐seq, many variations on the protocol have been proposed to extract unique and relevant information from biological samples. 3′ Tag‐Seq (also called TagSeq, 3′ Tag‐RNA‐Seq, and Quant‐Seq 3′ mRNA‐Seq) is one RNA‐seq variation where the 3′ end of the transcript is selected and amplified to yield one copy of cDNA from each transcript in the biological sample. We present a simple, easy‐to‐use, and publicly available computational workflow to analyze 3′ Tag‐Seq data. The workflow begins by trimming sequence adapters from raw FASTQ files. The trimmed sequence reads are checked for quality using FastQC and aligned to the reference genome, and then read counts are obtained using STAR. Differential gene expression analysis is performed using DESeq2, based on differential analysis of gene count data. The outputs of this workflow are MA plots, tables of differentially expressed genes, and UpSet plots. This protocol is intended for users specifically interested in analyzing 3′ Tag‐Seq data, and thus normalizations based on transcript length are not performed within the workflow. Future updates to this workflow could include custom analyses based on the gene counts table as well as data visualization enhancements. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.

Basic Protocol: Running the 3′ Tag‐Seq workflow

Support Protocol: Generating genome indices
Bulk and single‐cell spatial transcriptomic analysis reveals cuproptosis‐related molecular subtypes characterized by distinct tumour microenvironment infiltrates in colorectal cancer
Authors: Luo Wenqin , Gu Ruiqi , Fang Hongsheng , Zhang Ruijia , Gan Lu , Mo Shaobo , Li Qingguo
Published: February 2023

Background

The association between tumour microenvironment (TME) in colorectal cancer (CRC) and cell death patterns requires further exploration. Cuproptosis may provide new insight into analyzing CRC's TME.

Methods

We used cuproptosis‐related genes (CRGs) to stratify the meta‐Gene‐Expression Omnibus cohort by the “non‐negative matrix factorization” consistency matrix algorithm. To clarify the relative abundance of different cells in TME, CIBERSORT and single‐sample gene set enrichment methods were performed. Then, CRGs’ transcription in different cell types and the spatial position of CRGs’ enrichment were demonstrated through single‐cell spatial transcriptomics (STs) analysis. Prediction of clinical outcomes and response rate of immunotherapy was also conducted by constructing CRG_score.

Results

Three cuproptosis‐related TME phenotypes were figured out in CRC with distinctive clinicopathological and prognostic features. Three phenotypes were identical to immune‐inflamed, immune‐desert and immune‐excluded profiles, respectively. Interestingly, cuproptosis‐related cluster 3 (CPRC3) phenotype‐related gene_score was predominantly upregulated in the fibroblast region, consisting of stromal cells. This result was in line with CPRC3's immune‐excluded profile. Based on the robust cuproptosis‐related risk_score and nomogram, CRC patients’ clinical outcome and response to PD1/PD‐L1 immunotherapy can be well predicted.

Conclusions

This study characterized three cuproptosis‐related TME patterns with unique immune infiltration and prognosis in both bulk and single‐cell ST profiling. Risk_score was also built to help clinicians decide on personalized anticancer treatment and immunotherapy applications for CRC patients.
Comparison of fine‐needle aspiration and core‐needle biopsy in the pathological evaluation on thyroid lesions: A single‐center experience on 407 Chinese patients
Authors: Li Wei , Han Ya‐Ting , Hu Zhandong , Zhang Yujie , Zhao Xin , Guo Xuexi , Cai Wenjuan , Zhang Mingfang
Published: February 2023

Background

The object of this study was to compare the diagnosis performance of US‐guided fine‐needle aspiration (FNA) and core‐needle biopsy (CNB) for patients with thyroid nodules, in aspects of sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV).

Materials and Methods

Four hundred seven Chinese patients from July 2019 to June 2022 were retrospectively recruited in this study. Cytological diagnoses were categorized into six categories based on the 2017 Bethesda System for Reporting Thyroid Cytopathology (BSRTC), and histological specimens were drawn a diagnosis by means of an analogy with the Bethesda system.

Results

All patients incorporated were proceed with surgical excision (SE) and received final surgical diagnoses. The rate of malignancy (ROM) was comparable between two methods, with the exception that the test‐negative category of the FNA group was significantly higher than that of the CNB group (39.25% vs. 23.86%, p = .022). Sensitivity and accuracy were higher in CNB group (82.50% and 87.83%, respectively) than that in FNA group (72.00% and 79.36%, respectively), as well as NPV (76.14% in CNB vs. 60.75% in FNA), but not in terms of the specificity and PPV (95.59% and 97.30% in FNA vs. 97.10% and 98.02% in CNB).

Conclusion

CNB displayed a higher sensitivity and accuracy than FNA in malignant lesions of thyroid. Both FNA and CNB exhibit excellent performance with the understanding that both need to be applied under the most appropriate conditions to maximize their benefits.
Shikonin potentiates therapeutic efficacy of oxaliplatin through reactive oxygen species‐mediated intrinsic apoptosis and endoplasmic reticulum stress in oxaliplatin‐resistant colorectal cancer cells
Authors: Zhang Zhengguang , Shen Cunsi , Zhou Fuqiong , Zhang Yajie
Published: February 2023

Oxaliplatin (OXA) has been recognized as a third‐generation platinum‐based chemotherapeutic agent with stellar therapeutic efficacy in managing colorectal cancer (CRC). Nevertheless, resistance to OXA in CRC patients hinders its effectiveness. Shikonin (SHI), a natural naphthoquinone derived from Arnebia euchroma (Royle) Johnst., features a broad pharmacological profile and minimal toxicities. To assess the synergism of SHI and OXA towards OXA‐resistant CRC cells (HCT116R), we employed in vitro and in vivo pharmacological assays. Our experiments provided evidence that SHI, either alone or in combination with OXA, considerably reduced cell proliferation, triggered apoptosis, and induced the generation of reactive oxygen species (ROS) in HCT116R cells. Furthermore, the combination of SHI and OXA dramatically curbed the extent of HCT116R‐initiated xenograft growth in mouse models. Bioinformatics, western blot, and ROS assays highlighted that the mechanisms of SHI against OXA‐resistant CRC cells may involve the induction of cellular responses to chemical stress, intrinsic apoptosis, as well as endoplasmic reticulum stress pathways mediated by ROS. Notably, the synergism of SHI+OXA was partially abrogated by an ROS inhibitor N‐acetyl cysteine. Our findings imply the potential of SHI to boost the sensitivity of OXA to CRC, offering promising benefits for clinical strategies to combat OXA resistance.
Diastereoselective Synthesis of Camptothecin‐like Scaffolds: Construction of a New Class of Pseudo‐natural Products
Authors: Srikanth Gourishetty , Ravi Anil , Sebastian Anusha , Joseph Jobi , Khanfar Monther A. , El‐Gamal Mohammed I. , Al‐Qawasmeh Raed A. , Shehadi Ihsan A. , McN. Sieburth Scott , Abu‐Yousef Imad A. , Majdalawieh Amin F. , Al‐Tel Taleb H.
Published: February 2023

The discovery of novel small molecules endowed with high 3D‐content remains a powerful tool for interrogating underrepresented biological space. To this end, the pseudo‐natural products (pseudo‐NP) strategy has become one of the most important tools to deliver biologically significant chemical probes. In this article, we describe the development of a new class of pseudo‐NP collection, through connecting tryptamines with a furanose derivative followed by subjecting the product from this operation to a ring distortion strategy that led to diastereoselective synthesis of camptothecin‐like compounds. This process is driven by a cascade that unites Pictet–Spengler reaction with Michael addition reaction, followed by oxidative‐ring enlargement and subsequent transannular aldol cyclization delivering camptothecin‐like architectures. The obtained diastereoselectivity was verified using density functional theory (DFT) calculations.
A Modeling Approach for Assessing Ecological Risks of Neonicotinoid Insecticides from Emission to Nontarget Organisms: A Case Study of Cotton Plant
Authors: Li Zijian , Li Minmin , Niu Shan
Published: February 2023

The use of neonicotinoid insecticides in agriculture has posed threats to ecological systems, and there is a need to assess the ecological risks of neonicotinoids from emission to nontarget organisms. We introduced a modeling approach to assess the ecological risks of neonicotinoids using honeybee and earthworm as model organisms, and the simulation was flexible under different environmental conditions. Using the cotton plant as an example, the simulation results demonstrated that under current recommended application rates, the use of common neonicotinoid insecticides posed no threat to earthworms, with the simulated risk quotients (RQs) much lower than 1. However, the simulation for some neonicotinoid insecticides (e.g., acetamiprid) indicated that using these insecticides on cotton plants could threaten honeybees, with simulated RQs higher than 1. The variability analysis showed that in high-latitude regions, the unacceptable risk to honeybees posed by insecticide application can be further elevated due to cold, wet weather that results in relatively high insecticide levels in pollen and nectar. The model evaluation showed large overlaps of simulated risk intervals between the proposed and existing (BeeREX) models. Because the proposed and existing models have different simulation mechanisms, we recommend that these two models be used together to complement each other in future studies. Environ Toxicol Chem 2023;42:928–938. © 2023 SETAC
Cell‐instructive biomaterials in tissue engineering and regenerative medicine
Authors: Adhikari Bikram , Stager Michael A. , Krebs Melissa D.
Published: February 2023

The field of biomaterials aims to improve regenerative outcomes or scientific understanding for a wide range of tissue types and ailments. Biomaterials can be fabricated from natural or synthetic sources and display a plethora of mechanical, electrical, and geometrical properties dependent on their desired application. To date, most biomaterial systems designed for eventual translation to the clinic rely on soluble signaling moieties, such as growth factors, to elicit a specific cellular response. However, these soluble factors are often limited by high cost, convoluted synthesis, low stability, and difficulty in regulation, making the translation of these biomaterials systems to clinical or commercial applications a long and arduous process. In response to this, significant effort has been dedicated to researching cell‐directive biomaterials which can signal for specific cell behavior in the absence of soluble factors. Cells of all tissue types have been shown to be innately in tune with their microenvironment, which is a biological phenomenon that can be exploited by researchers to design materials that direct cell behavior based on their intrinsic characteristics. This review will focus on recent developments in biomaterials that direct cell behavior using biomaterial properties such as charge, peptide presentation, and micro‐ or nano‐geometry. These next generation biomaterials could offer significant strides in the development of clinically relevant medical devices which improve our understanding of the cellular microenvironment and enhance patient care in a variety of ailments.