bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strain evolution and novel downstream processing with integrated catalysis enable highly efficient coproduction of 1,3‐propanediol and organic acid esters from crude glycerol
Authors: Zhang Chijian , Sharma Shubhang , Ma Chengwei , Zeng An‐Ping 
Published: March 2022

AbstractBioconversion of natural microorganisms generally results in a mixture of various compounds. Downstream processing (DSP) which only targets a single product often lacks economic competitiveness due to incomplete use of raw material and high cost of waste treatment for by‐products. Here, we show with the efficient microbial conversion of crude glycerol by an artificially evolved strain and how a catalytic conversion strategy can improve the total products yield and process economy of the DSP. Specifically, Clostridium pasteurianum was first adapted to increased concentration of crude glycerol in a novel automatic laboratory evolution system. At m3 scale bioreactor the strain achieved a simultaneous production of 1,3‐propanediol (PDO), acetic and butyric acids at 81.21, 18.72, and 11.09 g/L within only 19 h, respectively, representing the most efficient fermentation of crude glycerol to targeted products. A heterogeneous catalytic step was developed and integrated into the DSP process to obtain high‐value methyl esters from acetic and butyric acids at high yields. The coproduction of the esters also greatly simplified the recovery of PDO. For example, a cosmetic grade PDO (96% PDO) was easily obtained by a simple single‐stage distillation process (with an overall yield more than 77%). This integrated approach provides an industrially attractive route for the simultaneous production of three appealing products from the crude glycerol fermentation broth, which greatly improve the process economy and ecology.
CRISPR‐Mediated Enzyme Fragment Complementation Assay for Quantification of the Stability of Splice Isoforms
Authors: Tang Zhichao , Hegde Shalakha , Zhao Junxing , Zhu Shoutian , Johnson Kristen A. , Lorson Christian L. , Wang Jingxin 
Published: March 2022

AbstractSmall‐molecule splicing modulators exemplified by an FDA‐approved drug, risdiplam, are a new pharmacological modality for regulating the expression and stability of splice isoforms. We report a CRISPR‐mediated enzyme fragment complementation (EFC) assay to quantify the splice isoform stability. The EFC assay harnessed a 42 amino acid split of a β‐galactosidase (designate α‐tag), which could be fused at the termini of the target genes using CRISPR/cas9. The α‐tagged splice isoform would be quantified by measuring the enzymatic activity upon complementation with the rest of β‐galactosidase. This EFC assay retained all the sequences of introns and exons of the target gene in the native genomic environment that recapitulates the cell biology of the diseases of interest. For a proof‐of‐concept, we developed a CRISPR‐mediated EFC assay targeting the exon 7 of the survival of motor neuron 2 (SMN2) gene. The EFC assay is compatible with 384‐well plates and robustly quantified the splicing modulation activity of small molecules. In this study, we also discovered that a coumarin derivative, compound 4, potently modulated SMN2 exon 7 splicing at as low as 1.1 nM.
The biological effects of geomagnetic field exhibit an important potential for cancer and vascular diseases
Authors: Chen Enlin , Chen Zhe , Chen Linxi , Hu Xiaoling 
Published: March 2022

AbstractXu et al. recently demonstrated that cryptochrome 4 (CRY4) protein, as a light‐dependent magnetic receptor, can sense geomagnetic fields to guide night‐migratory songbirds' navigation and evolution by the formation of composite radical pairs and electron transport. We aim to comment on CRY4 through radical pairs and electron transport for magnetic sensitive in night‐migratory songbirds' migration and evolution. Additionally, we find that the role of magnetic fields is deeply concerning to the scientific community and very enlightening for the diagnosis and treatment of cancer and vascular disease. We believe that this commentary makes a significant contribution to the literature because it elaborates on the importance of the geomagnetic field to night‐migratory songbirds and extends the diagnostic and therapeutic value to cancer and vascular disease.
Prosthetic valve endocarditis: Literally a growing concern following transcatheter aortic valve replacement
Authors: Goldsweig Andrew M. , Baron Suzanne J. 
Published: March 2022

Key Points

Prosthetic valve endocarditis (PVE) following transcatheter aortic valve replacement (TAVR) in low surgical risk patients is uncommon, occurring in 11 of 396 patients (2.8%) in the study by Medranda et al., but associated with high morbidity (6 of 11 with embolic strokes [55%]) and mortality (2 of 11 [18%]).
As TAVR volumes increase, especially in low surgical risk patients, whose long‐term outcomes are generally excellent, PVE will become an increasingly important concern.
Future research is needed to identify optimal strategies for prevention, diagnosis, and treatment of PVE associated with TAVR.
Atypical presentation of adenosine deaminase 2 deficiency with bi‐allelic ADA2 mutation
Authors: Al‐shaikh Reem , Alnowaiser Dimah , Peer‐Zada Abdul Ali , Almutairi Awatif , Alghamdi Hamza 
Published: March 2022

AbstractHerein, we report a case of VAIHS with atypical clinical presentation of perianal abscess, fistula fever, and bi‐cytopenia including pathogenic ADA2 mutation suggesting that ADA2 deficiency be considered as a differential diagnosis of enlarging cutaneous abscess with no evidence of wound healing in the setting of leukopenia and neutropenia.
Metalloimmunotherapy with Rhodium and Ruthenium Complexes: Targeting Tumor‐Associated Macrophages
Authors: Toupin Nicholas , Herroon Mackenzie K. , Thummel Randolph P. , Turro Claudia , Podgorski Izabela , Gibson Heather , Kodanko Jeremy J. 
Published: March 2022

AbstractTumor associated macrophages (TAMs) suppress the cancer immune response and are a key target for immunotherapy. The effects of ruthenium and rhodium complexes on TAMs have not been well characterized. To address this gap in the field, a panel of 22 dirhodium and ruthenium complexes were screened against three subtypes of macrophages, triple‐negative breast cancer and normal breast tissue cells. Experiments were carried out in 2D and biomimetic 3D co‐culture experiments with and without irradiation with blue light. Leads were identified with cell‐type‐specific toxicity toward macrophage subtypes, cancer cells, or both. Experiments with 3D spheroids revealed complexes that sensitized the tumor models to the chemotherapeutic doxorubicin. Cell surface exposure of calreticulin, a known facilitator of immunogenic cell death (ICD), was increased upon treatment, along with a concomitant reduction in the M2‐subtype classifier arginase. Our findings lay a strong foundation for the future development of ruthenium‐ and rhodium‐based chemotherapies targeting TAMs.
Electrochemically Driven Swinging of a Nitrobenzyl Pendant Arm in a Nickel Scorpionand Complex
Authors: Ciarrocchi Carlo , Fabbrizzi Luigi , Licchelli Maurizio , Taglietti Angelo 
Published: March 2022

AbstractA radical anion −NO2.− is formed upon an electrochemically reversible one‐electron reduction of the square‐planar NiII complex of N‐nitrobenzylcyclam. The −NO2.− group goes to occupy an axial position of the metal ion, thus establishing a significant electronic interaction with the metal center. In particular, the ESR spectrum supports the occurrence of an electron transfer from −NO2.− to the metal, which therefore presents a significant NiI character. On re‐oxidation, the nitrobenzyl side chain detaches and the NiII complex is restored, providing an example of a fully reversible redox driven intramolecular motion.
Mechanistic Insights into the Photoisomerization of N,N′‐Disubstituted Indigos
Authors: Budzák Šimon , Jovaišaitė Justina , Huang Chung‐Yang , Baronas Paulius , Tulaitė Kamilė , Juršėnas Saulius , Jacquemin Denis , Hecht Stefan 
Published: March 2022

AbstractN,N′‐disubstituted indigos are photoswitchable molecules that have recently caught the attention due to their addressability by red‐light. When alkyl and aryl groups are utilized as the N‐substituents, the thermal half‐lives of Z isomers can be tuned independently while maintaining the advantageous red‐shifted absorption spectra. To utilize these molecules in real‐world applications, it is of immense importance to understand how their molecular structures as well as the environment influence their switching properties. To this end, we probed their photoisomerization mechanism by carrying out photophysical and computational studies in solvents of different polarities. The fluorescence and transient absorption experiments suggest for more polar excited and transition states, which explains the bathochromic shifts of absorption spectra and shorter thermal half‐lives. On the other hand, the quantum chemical calculations reveal that in contrast to N‐carbonyl groups, N‐alkyl and N‐aryl substituents are not strongly conjugated with the indigo chromophore and can thus serve as a tool for tuning the thermal stability of Z isomers. Both approaches are combined to provide in‐depth understandings of how indigos undergo photoswitching as well as how they are influenced by N‐substituent and the chemical surroundings. These mechanistic insights will serve as guiding principles for designing molecules eyeing broader applications.
Polymerization kinetics of tubulin from mung seedlings modeled as a competition between nucleation and GTP‐hydrolysis rates
Authors: Jain Kunalika , Basu Jashaswi , Roy Megha , Yadav Jyoti , Patil Shivprasad , Athale Chaitanya A. 
Published: March 2022

AbstractMicrotubules (MTs) form physiologically important cytoskeletal structures that are assembled by tubulin polymerization in nucleation‐ and guanosine triphosphate (GTP)‐dependent manner. GTP hydrolysis competes with the addition of monomers, to determine the GTP‐cap size, and the onset of shrinkage, which alternates with growth. Multiple theoretical models of MT polymerization dynamics have been reconciled to the kinetics of animal brain tubulins, but more recently, rapid kinetics seen in Arabidopsis tubulin polymerization suggest the need to sample a wider diversity in tubulin polymerization kinetics and reconcile it to theory. Here, we isolated tubulin from seedlings of Vigna sp. (mung bean), compared polymerization kinetics to animal brain tubulin, and used a computational model to understand the differences. We find that activity‐isolated mung tubulin polymerizes in a nucleation‐dependent manner, based on turbidimetry, qualitatively similar to brain tubulin, but with a 10‐fold smaller critical concentration. GTP‐dependent polymerization kinetics also appear to be transient, indicative of high rates of GTP hydrolysis. Computational modeling of tubulin nucleation and vectorial GTP hydrolysis to examine the effects of high nucleation and GTP‐hydrolysis rates predicts a dominance of the latter in determining MT lengths and numbers. Microscopy of mung tubulin filaments stabilized by GMPCPP or taxol results in few and short MTs, compared to the many long MTs arising from goat tubulin, qualitatively matching the model predictions. We find GTP‐hydrolysis outcompetes nucleation rates in determining MT lengths and numbers.
Dealloying Synthesis of Silicon Nanotubes for High‐Performance Lithium Ion Batteries
Authors: Zhao Jinfu , Wei Wenxian , Xu Na , Wang Xiaotong , Chang Limin , Wang Li , Fang Luan , Le Zaiyuan , Nie Ping 
Published: March 2022

AbstractPractical applications of silicon‐based anodes in lithium ion batteries have attracted unprecedented attentions due to the merits of extraordinary energy density, high safety and low cost. Nevertheless, the inevitable huge volume change upon lithiation and delithiation brings about silicon electrode integrity damage and fast capacity fading, hampering the large‐scale application. Herein, a novel one‐dimensional tubular silicon‐nitrogen doped carbon composite (Si@NC) with a core‐shell structure has been fabricated using silicon magnesium alloy and polydopamine as a template and precursor. The as‐obtained composite exhibits remarkable specific capacity and ultrafast redox kinetics, an outstanding cycling stability with fine capacity of 583.6 mAh g−1 at 0.5 A g−1 over 200 cycles is delivered. Moreover, a full cell matched with LiFePO4 cathode has demonstrated a reversible capacity of 148.8 mAh g−1 with high Coulombic efficiency as well as an excellent energy density of 396 Wh kg−1. The nanotube structure engineering and silicon confined in nitrogen doped carbon effectively alleviate the volume expansion and endow the composite with superior stability. The robust strategy developed here gives a new insight into designing silicon anodes for enhanced lithium storage properties.
Stand up for Electrostatics: The Disiloxane Case
Authors: Martín‐Fernández Carlos , Alkorta Ibon , Montero‐Campillo M. Merced , Elguero José 
Published: March 2022

AbstractThe basicity of the simplest silicone, disiloxane (H3Si−O−SiH3), is strongly affected by the Si−O−Si angle (α). We use high‐level ab initio MP2/aug′‐cc‐pVTZ calculations and the molecular electrostatic potential (MEP) to analyze the relationship between the increase in basicity and the reduction of α. Our results clearly point out that this increase can be explained through the MEP, as the interactions between oxygen from disiloxane and the acceptors are mostly electrostatic. Furthermore, the effect of α on the tetrel bond between disiloxane and several Lewis bases can again be rationalized using the MEP. Finally, we explore the cooperativity throughout α for ternary complexes where disiloxane simultaneously interacts with a Lewis acid and a Lewis base. Both non‐covalent interactions remain cooperative for all α values, although the largest cooperativity effects are not always those maximizing the binding energy in the binary complexes. Overall, the MEP remains a powerful predictor for noncovalent interactions.
The influence of training variables on lingual strength and swallowing in adults with and without dysphagia
Authors: Abe Takashi , Viana Ricardo B. , Wong Vickie , Bell Zachary W. , Spitz Robert W. , Yamada Yujiro , Thiebaud Robert S. , Loenneke Jeremy P. 
Published: March 2022

AbstractBackgroundSwallowing disorders (dysphagia) occur in a large proportion of individuals over the age of 60. The improvement of tongue strength by resistance exercise is postulated to be directly related to lingual‐palatal pressure generation and bolus propulsion into the pharynx during swallowing. To the best of our knowledge, however, there is no evidence‐based discussion evaluating the strength training variables of the tongue for improving tongue strength maximally.MethodsTo solve this problem, we reviewed the relationships between different resistance training variables (i.e. training period, intensity, duration of muscle contraction, volume, and frequency) and the change in muscle strength in the lingual muscle.ResultsOur findings show that tongue strength training may improve anterior and posterior tongue strength in both healthy adults and patients with dysphagia. Anterior and posterior tongue strength gradually increased and did not reach a plateau after at least 8 weeks of training. Data for other variables were insufficient to draw clear conclusions. Available data suggest that a training intensity of 60–100% of maximum tongue strength, a contraction time of 2–3 s, a total number of 90–120 repetitions per day, and a training frequency of three times per week appears to result in an improvement in maximal isometric tongue elevation strength in adults with and without dysphagia.ConclusionsFuture studies are warranted to better determine if there are dose–response relationships in tongue strength training in healthy adults and patients with dysphagia.
Significance of fluid retention, body mass index, and weight loss in patients with advanced cancer
Authors: Amano Koji , Maeda Isseki , Ishiki Hiroto , Miura Tomofumi , Hatano Yutaka , Oya Kiyofumi , Sakashita Akihiro , Ito Satoko , Hiratsuka Yusuke , Morita Tatsuya , Mori Masanori 
Published: March 2022

AbstractBackgroundFew studies have investigated the relationship between body mass index (BMI) and mortality or evaluated the prognostic validity of a grading system incorporating BMI and weight loss in Asian cancer patients. We conducted a study to investigate characteristics according to BMI and to confirm the prognostic validity of BMI and the grading system.MethodsThis study involved a secondary analysis of a prospective cohort study. Subjects were divided into six BMI groups and five grades according to the grading system. Characteristics were compared between the six groups. We conducted time‐to‐event analyses using the Kaplan–Meier method, log‐rank test, and univariate and multivariate Cox regression analyses.ResultsA total of 1094 patients were classified into six BMI groups: <17 (n = 244), 17–18.4 (n = 211), 18.5–19.9 (n = 192), 20–21.9 (n = 196), 22–24.9 (n = 161), and 25 ≤ (n = 90). Regarding oedema, the prevalence increased with BMI, being 70% the 25 ≤ group. The prevalence of pleural effusion and ascites were the highest in the 25 ≤ group. Median survival ranged between 18 and 22 days in the six groups. No significant differences were observed in survival rates among the six BMI groups (log rank P = 0.83). No significant differences were observed in survival rates among the five grades (log rank P = 0.25).ConclusionsThe prevalence of fluid retention is high in patients with advanced cancer. BMI and weight loss appear to lose their prognostic significance among them.
Denervation‐induced loss of skeletal muscle mass influences immune homeostasis and accelerates the disease progression of lupus nephritis
Authors: Liu Shuang , Kiyoi Takeshi , Takemasa Erika , Mogi Masaki 
Published: March 2022

AbstractBackgroundPatients with systemic autoimmune disease are predisposed to developing sarcopenia associated with their underlying proinflammatory condition and a decrease in motility. How sarcopenic status affects disease progression remains unknown. The present study explored the influence of denervation‐induced sarcopenia on immune homeostasis and investigated related biological pathways that might be important for future disease management.MethodsA denervation‐induced skeletal muscle loss model was established, and the function of the immune system was evaluated. Immune cell proportions and cytokine levels in peripheral blood and atrophied skeletal muscle were profiled. We examined store‐operated Ca2+ entry and mitochondrial function in immune cells. MRL/lpr mice were used to evaluate the influence of denervation‐induced sarcopenia on autoimmune progression in lupus nephritis.ResultsCompared with splenocyte fractions obtained from sham mice, proportions of CD4+ cells, CD8+ cells, CD19+CD20− cells, CD49b+NK46+ cells, CD4+IL‐4+ cells, and CD4+FoxP3+ cells were significantly decreased, whereas CD19+CD20+ cells, CD4+IFN‐γ+ cells, and CD4+IL17+ cells were markedly increased in sciatic nerve axotomy (SNA) mice. The serum cytokine profile indicated that SNA significantly increased the protein expressions of IL‐12p70 (P = 0.014), IL‐17A (P = 0.007), and IFN‐γ (P < 0.001). In SNA mice, there was an 18.74% decrease in peak Ca2+ influx (P < 0.001) and an 18.22% decrease in initial Ca2+ influx (P < 0.001) rates in peripheral T cells compared with sham mice. Mitochondrial respiration was significantly reduced in peripheral T cells from SNA mice compared with sham mice. SNA substantially promoted disease progression in lupus model mice demonstrated by the results of proteinuria monitoring, serum levels of blood urea nitrogen, and kidney histological scores.ConclusionsThe loss of skeletal muscle impaired mitochondrial respiration and activation in T cells and influenced the balance of T helper cell subsets. Therefore, denervation‐induced sarcopenia might promote the progression of autoimmune diseases, such as lupus nephritis, and enhance Th1/Th17 functions. These results suggest that physicians should be aware of the impact of the loss of skeletal muscle on the management of autoimmune disease and that a multidisciplinary approach is required to minimize the overall adverse impact of sarcopenia.
The utility of the ultrasonographic assessment of the lower leg muscles to evaluate sarcopenia and muscle quality in older adults
Authors: Isaka Masaaki , Sugimoto Ken , Fujimoto Taku , Yasunobe Yukiko , Xie Keyu , Onishi Yuri , Yoshida Shino , Takahashi Toshimasa , Kurinami Hitomi , Akasaka Hiroshi , Takeya Yasushi , Yamamoto Koichi , Rakugi Hiromi 
Published: March 2022

AbstractBackgroundThe assessment of muscle quality is expected to help predict the prognosis of sarcopenia and examine the response to intervention. Ultrasonography can be used to evaluate approaches for determining muscle quantity and quality. We focused on the lower leg muscles and examined the relationship between the ultrasonographic assessments and the components of sarcopenia and muscle quality by comparing them with those of the quadriceps muscle (QFM).Methods47 physically healthy older participants aged 78.3 ± 6.0 years (53% male) were enrolled in this cross‐sectional study. Muscle thickness (MT) and echo intensity (EI) of the lower leg muscles and QFM were assessed with ultrasonography. Muscle mass, grip strength, and gait speed, and lower leg muscle strength were measured. Muscle quality was calculated using a formula: leg muscle strength/leg muscle mass.ResultsThe MTs and EIs of the tibialis anterior muscle (TA) and QFM were significantly associated with grip and leg strength. We observed a significant correlation in the MTs and EIs of the lower leg muscles and QFM. The EIs of the lower leg muscles and QFM showed significant negative correlations with muscle quality. In the multiple linear regression model, the EI of the TA and QFM was extracted as an independent factor of muscle quality (TA: β = −0.35, p = 0.0358; QFM: β = −0.30, p = 0.0327).ConclusionsThe ultrasonographic assessments of the lower leg muscles, especially the TA, were associated with sarcopenia components and muscle quality equal to or greater than those of the QFM.
Ultrasound imaging for measuring muscle and subcutaneous fat tissue thickness of the anterior thigh: a 2 year longitudinal study in middle age
Authors: Mechelli Filippo , Arendt‐Nielsen Lars , Stokes Maria , Agyapong‐Badu Sandra 
Published: March 2022

AbstractBackgroundUltrasound (US) imaging technique is widely used in research and clinical settings to assess the morphology and morphometry of neuromusculoskeletal structures. The technique has reported validity and reliability in measuring the size of various muscles under controlled conditions. The aim of the present study was to assess anterior thigh thickness using US imaging, in a healthy cohort of middle‐aged older adults.MethodsParticipants included 17 healthy older adults involved in regular moderate‐vigorous activities (age range 39–66 years). US imaging scans of the anterior thighs 2 years since baseline measurements were performed. Images were analysed offline to compare US imaging measurements of muscle thickness and subcutaneous fat (SF) of the anterior thigh taken at baseline and after 2 years.ResultsThere was no significant difference between muscle thickness measurements taken at baseline and after 2 years (mean, standard deviation; baseline = 2.80 ± 0.71 cm; follow‐up = 2.77 ± 0.72 cm, P = 0.33). There was also no significant change in SF thickness (baseline = 1.04 ± 0.41 cm; follow‐up = 1.06 ± 0.40, P = 0.33).ConclusionsThe results show that there was no decline in anterior thigh muscle thickness or increase in SF in the healthy cohort studied using US imaging over a 2 year period. These findings demonstrate the robustness of US imaging measurements over time.