bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent advances in double-lumen tube malposition in thoracic surgery: A bibliometric analysis and narrative literature review
Authors: Zhang Xi , Wang Dong-Xu , Wei Jing-Qiu , Liu He , Hu Si-Ping
Published: December 2022

Thoracic surgery has increased drastically in recent years, especially in light of the severe outbreak of the 2019 novel coronavirus disease (COVID-19). Routine “passive” chest computed tomography (CT) screening of inpatients detects some pulmonary diseases requiring thoracic surgeries timely. As an essential device for thoracic anesthesia, the double-lumen tube (DLT) is particularly important for anesthesia and surgery. With the continuous upgrading of the DLTs and the widespread use of fiberoptic bronchoscopy (FOB), the position of DLT in thoracic surgery is gradually becoming more stable and easier to observe or adjust. However, DLT malposition still occurs during transferring patients from a supine to the lateral position in thoracic surgery, which leads to lung isolation failure and hypoxemia during one-lung ventilation (OLV). Recently, some innovative DLTs or improved intervention methods have shown good results in reducing the incidence of DLT malposition. This review aims to summarize the recent studies of the incidence of left-sided DLT malposition, the reasons and effects of malposition, and summarize current methods for reducing DLT malposition and prospects for possible approaches. Meanwhile, we use bibliometric analysis to summarize the research trends and hot spots of the DLT research.
Whether interstitial space features were the main factors affecting sediment microbial community structures in Chaohu Lake
Authors: Lu Xiang , Zhou Xiaotian , von Sperber Christian , Xu Yaofei , Wei Zhipeng , Li Siyan , Ruan Aidong
Published: December 2022

Sediments cover a majority of Earth’s surface and are essential for global biogeochemical cycles. The effects of sediment physiochemical features on microbial community structures have attracted attention in recent years. However, the question of whether the interstitial space has significant effects on microbial community structures in submerged sediments remains unclear. In this study, based on identified OTUs (operational taxonomic units), correlation analysis, RDA analysis, and Permanova analysis were applied into investigating the effects of interstitial space volume, interstitial gas space, volumetric water content, sediment particle features (average size and evenness), and sediment depth on microbial community structures in different sedimentation areas of Chaohu Lake (Anhui Province, China). Our results indicated that sediment depth was the closest one to the main environmental gradient. The destruction effects of gas space on sediment structures can physically affect the similarity of the whole microbial community in all layers in river dominated sedimentation area (where methane emits actively). However, including gas space, none of the five interstitial space parameters were significant with accounting for the microbial community structures in a sediment layer. Thus, except for the happening of active physical destruction on sediment structures (for example, methane ebullition), sediment interstitial space parameters were ineffective for affecting microbial community structures in all sedimentation areas.
High-throughput sequencing reveals the presence of novel and known viruses in diseased Paris yunnanensis
Authors: Lan Ping-xiu , He Peng , Yang Jie , Zhou Guo-hua , Chen Xiao-jiao , Wei Tai-yun , Li Chen-rong , Gu Rong , Li Ruhui , Li Fan
Published: December 2022

Paris spp. are important medicinal plant and main raw material for many Chinese patent medicines, but viral diseases have became serious problems in cultivation of this group of important medicinal plants in China. In this study, eight viruses were identified in the diseased plants of Paris yunnanensis by high-throughput sequencing (HTS) and RT–PCR. These viruses include three novel viruses (two potyviruses and one nepovirus), Hippeastrum chlorotic ringspot virus (HCRV), Lychnis mottle virus (LycMoV), Paris mosaic necrosis virus (PMNV), Paris virus 1 and pepper mild mottle virus. The three new viruses were tentatively named Paris potyvirus 3 (ParPV-3), Paris potyvirus 4 (ParPV-4), Paris nepovirus 1 (ParNV-1) and their complete genome sequences were determined. Sequence analyses showed ParPV-3 and ParPV-4 shared the highest amino acid (aa) sequence identities of 54.3% to each other and 53.0–57.8% to other known potyviruses. ParNV-1 had aa sequence identities of 28.8–63.7% at protease-polymerase (Pro-Pol) with other nepoviruses. Phylogenetic analyses further support that the three viruses are new members of their corresponding genera. Analyses of the partial sequences of HCRV and LycMoV infecting P. yunnanensis revealed they diverged from existing isolates by aa sequence identities of 97.1% at glycoprotein precursor of HCRV and 93.3% at polyprotein of LycMoV. These two viruses are reported for the first time in Paris spp. A total of 123 field samples collected from P. yunnanensis in four counties of Yunnan, Southwest China were tested by RT–PCR for detecting each of the eight viruses. Results showed that nearly half of the samples were positive for at least one of the eight viruses. Two potyviruses, ParPV-3 (26.8%) and PMNV (24.4%), were predominant and widely distributed in the fields, while other viruses occurred in low rates and/or had limited distribution. This study insights into the virome infecting P. yunnanensis and provides valuable information for diagnosis and control of viral diseases in P. yunnanensis.
Crystal polymorphism in fragment-based lead discovery of ligands of the catalytic domain of UGGT, the glycoprotein folding quality control checkpoint
Authors: Caputo Alessandro T. , Ibba Roberta , Le Cornu James D. , Darlot Benoit , Hensen Mario , Lipp Colette B. , Marcianò Gabriele , Vasiljević Snežana , Zitzmann Nicole , Roversi Pietro
Published: December 2022

None of the current data processing pipelines for X-ray crystallography fragment-based lead discovery (FBLD) consults all the information available when deciding on the lattice and symmetry (i.e., the polymorph) of each soaked crystal. Often, X-ray crystallography FBLD pipelines either choose the polymorph based on cell volume and point-group symmetry of the X-ray diffraction data or leave polymorph attribution to manual intervention on the part of the user. Thus, when the FBLD crystals belong to more than one crystal polymorph, the discovery pipeline can be plagued by space group ambiguity, especially if the polymorphs at hand are variations of the same lattice and, therefore, difficult to tell apart from their morphology and/or their apparent crystal lattices and point groups. In the course of a fragment-based lead discovery effort aimed at finding ligands of the catalytic domain of UDP–glucose glycoprotein glucosyltransferase (UGGT), we encountered a mixture of trigonal crystals and pseudotrigonal triclinic crystals—with the two lattices closely related. In order to resolve that polymorphism ambiguity, we have written and described here a series of Unix shell scripts called CoALLA (crystal polymorph and ligand likelihood-based assignment). The CoALLA scripts are written in Unix shell and use autoPROC for data processing, CCP4-Dimple/REFMAC5 and BUSTER for refinement, and RHOFIT for ligand docking. The choice of the polymorph is effected by carrying out (in each of the known polymorphs) the tasks of diffraction data indexing, integration, scaling, and structural refinement. The most likely polymorph is then chosen as the one with the best structure refinement Rfree statistic. The CoALLA scripts further implement a likelihood-based ligand assignment strategy, starting with macromolecular refinement and automated water addition, followed by removal of the water molecules that appear to be fitting ligand density, and a final round of refinement after random perturbation of the refined macromolecular model, in order to obtain unbiased difference density maps for automated ligand placement. We illustrate the use of CoALLA to discriminate between H3 and P1 crystals used for an FBLD effort to find fragments binding to the catalytic domain of Chaetomium thermophilum UGGT.
Neuroanatomical and psychological considerations in temporal lobe epilepsy
Authors: DeFelipe Javier , DeFelipe-Oroquieta Jesús , Furcila Diana , Muñoz-Alegre Mar , Maestú Fernando , Sola Rafael G. , Blázquez-Llorca Lidia , Armañanzas Rubén , Kastanaskaute Asta , Alonso-Nanclares Lidia , Rockland Kathleen S. , Arellano Jon I.
Published: December 2022

Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy and is associated with a variety of structural and psychological alterations. Recently, there has been renewed interest in using brain tissue resected during epilepsy surgery, in particular ‘non-epileptic’ brain samples with normal histology that can be found alongside epileptic tissue in the same epileptic patients — with the aim being to study the normal human brain organization using a variety of methods. An important limitation is that different medical characteristics of the patients may modify the brain tissue. Thus, to better determine how ‘normal’ the resected tissue is, it is fundamental to know certain clinical, anatomical and psychological characteristics of the patients. Unfortunately, this information is frequently not fully available for the patient from which the resected tissue has been obtained — or is not fully appreciated by the neuroscientists analyzing the brain samples, who are not necessarily experts in epilepsy. In order to present the full picture of TLE in a way that would be accessible to multiple communities (e.g., basic researchers in neuroscience, neurologists, neurosurgeons and psychologists), we have reviewed 34 TLE patients, who were selected due to the availability of detailed clinical, anatomical, and psychological information for each of the patients. Our aim was to convey the full complexity of the disorder, its putative anatomical substrates, and the wide range of individual variability, with a view toward: (1) emphasizing the importance of considering critical patient information when using brain samples for basic research and (2) gaining a better understanding of normal and abnormal brain functioning. In agreement with a large number of previous reports, this study (1) reinforces the notion of substantial individual variability among epileptic patients, and (2) highlights the common but overlooked psychopathological alterations that occur even in patients who become “seizure-free” after surgery. The first point is based on pre- and post-surgical comparisons of patients with hippocampal sclerosis and patients with normal-looking hippocampus in neuropsychological evaluations. The second emerges from our extensive battery of personality and projective tests, in a two-way comparison of these two types of patients with regard to pre- and post-surgical performance.
Audiovisual integration of the dynamic hand-held tool at different stimulus intensities in aging
Authors: Yang Weiping , Yang Xiangfu , Guo Ao , Li Shengnan , Li Zimo , Lin Jinfei , Ren Yanna , Yang Jiajia , Wu Jinglong , Zhang Zhilin
Published: December 2022

Introduction: In comparison to the audiovisual integration of younger adults, the same process appears more complex and unstable in older adults. Previous research has found that stimulus intensity is one of the most important factors influencing audiovisual integration.

Methods: The present study compared differences in audiovisual integration between older and younger adults using dynamic hand-held tool stimuli, such as holding a hammer hitting the floor. Meanwhile, the effects of stimulus intensity on audiovisual integration were compared. The intensity of the visual and auditory stimuli was regulated by modulating the contrast level and sound pressure level.

Results: Behavioral results showed that both older and younger adults responded faster and with higher hit rates to audiovisual stimuli than to visual and auditory stimuli. Further results of event-related potentials (ERPs) revealed that during the early stage of 60–100 ms, in the low-intensity condition, audiovisual integration of the anterior brain region was greater in older adults than in younger adults; however, in the high-intensity condition, audiovisual integration of the right hemisphere region was greater in younger adults than in older adults. Moreover, audiovisual integration was greater in the low-intensity condition than in the high-intensity condition in older adults during the 60–100 ms, 120–160 ms, and 220–260 ms periods, showing inverse effectiveness. However, there was no difference in the audiovisual integration of younger adults across different intensity conditions.

Discussion: The results suggested that there was an age-related dissociation between high- and low-intensity conditions with audiovisual integration of the dynamic hand-held tool stimulus. Older adults showed greater audiovisual integration in the lower intensity condition, which may be due to the activation of compensatory mechanisms.
Dll1 haploinsufficiency causes brain abnormalities with functional relevance
Authors: Arzate Dulce-María , Valencia Concepción , Dimas Marco-Antonio , Antonio-Cabrera Edwards , Domínguez-Salazar Emilio , Guerrero-Flores Gilda , Gutiérrez-Mariscal Mariana , Covarrubias Luis
Published: December 2022

Introduction

The Notch pathway is fundamental for the generation of neurons during development. We previously reported that adult mice heterozygous for the null allele of the gene encoding the Delta-like ligand 1 for Notch (Dll1lacZ) have a reduced neuronal density in the substantia nigra pars compacta. The aim of the present work was to evaluate whether this alteration extends to other brain structures and the behavioral consequences of affected subjects.

Methods

Brains of Dll1+/lacZ embryos and mice at different ages were phenotypically compared against their wild type (WT) counterpart. Afterwards, brain histological analyses were performed followed by determinations of neural cell markers in tissue slices. Neurological deficits were diagnosed by applying different behavioral tests to Dll1+/lacZ and WT mice.

Results

Brain weight and size of Dll1+/lacZ mice was significantly decreased compared with WT littermates (i.e., microcephaly), a phenotype detected early after birth. Interestingly, enlarged ventricles (i.e., hydrocephalus) was a common characteristic of brains of Dll1 haploinsufficient mice since early ages. At the cell level, general cell density and number of neurons in several brain regions, including the cortex and hippocampus, of Dll1+/lacZ mice were reduced as compared with those regions of WT mice. Also, fewer neural stem cells were particularly found in the adult dentate gyrus of Dll1+/lacZ mice but not in the subventricular zone. High myelination levels detected at early postnatal ages (P7–P24) were an additional penetrant phenotype in Dll1+/lacZ mice, observation that was consistent with premature oligodendrocyte differentiation. After applying a set of behavioral tests, mild neurological alterations were detected that caused changes in motor behaviors and a deficit in object categorization.

Discussion

Our observations suggest that Dll1 haploinsufficiency limits Notch signaling during brain development which, on one hand, leads to reduced brain cell density and causes microcephaly and hydrocephalus phenotypes and, on the other, alters the myelination process after birth. The severity of these defects could reach levels that affect normal brain function. Therefore, Dll1 haploinsufficiency is a risk factor that predisposes the brain to develop abnormalities with functional consequences.
Living on the edge: How to prepare for it?
Authors: Van Puyvelde Martine , Gijbels Daisy , Van Caelenberg Thomas , Smith Nathan , Bessone Loredana , Buckle-Charlesworth Susan , Pattyn Nathalie
Published: December 2022

Introduction

Isolated, confined, and extreme (ICE) environments such as found at Antarctic, Arctic, and other remote research stations are considered space-analogs to study the long duration isolation aspects of operational space mission conditions.

Methods

We interviewed 24 sojourners that participated in different short/long duration missions in an Antarctic (Concordia, Halley VI, Rothera, Neumayer II) or non-Antarctic (e.g., MDRS, HI-SEAS) station or in polar treks, offering a unique insight based on first-hand information on the nature of demands by ICE-personnel at multiple levels of functioning. We conducted a qualitative thematic analysis to explore how sojourners were trained, prepared, how they experienced the ICE-impact in function of varieties in environment, provided trainings, station-culture, and type of mission.

Results

The ICE-environment shapes the impact of organizational, interpersonal, and individual working- and living systems, thus influencing the ICE-sojourners' functioning. Moreover, more specific training for operating in these settings would be beneficial. The identified pillars such as sensory deprivation, sleep, fatigue, group dynamics, displacement of negative emotions, gender-issues along with coping strategies such as positivity, salutogenic effects, job dedication and collectivistic thinking confirm previous literature. However, in this work, we applied a systemic perspective, assembling the multiple levels of functioning in ICE-environments.

Discussion

A systemic approach could serve as a guide to develop future preparatory ICE-training programs, including all the involved parties of the crew system (e.g., family, on-ground crew) with attention for the impact of organization- and station-related subcultures and the risk of unawareness about the impact of poor sleep, fatigue, and isolation on operational safety that may occur on location.
Dietary inflammatory index, and depression and mortality risk associations in U.S. adults, with a special focus on cancer survivors
Authors: Zhang Yuzheng , Wu Yanhua , Zhang Yangyu , Cao Donghui , He Hua , Cao Xueyuan , Wang Yuehui , Jia Zhifang , Jiang Jing
Published: December 2022

Introduction

A higher risk for depression and mortality is associated with the inflammatory potential of diet measured through the Dietary Inflammatory Index (DII). The roles of DII in the risk of depression and death in cancer survivors were unclear. We aimed to examine the association between energy-adjusted DII (E-DII) score and risk of depression, and mortality using data from the 2007–2018 National Health and Nutrition Examination Survey (NHANES), with a special focus on cancer survivors.

Methods

The 24-h dietary recall interview was used as a basis to calculate the E-DII score and the Patient Health Questionnaire-9 (PHQ-9) was used to measure the depressive outcomes. Logistic regression analyses were performed to determine the association between quartiles of E-DII score and depression. Cox proportional hazard regression and competing risk analyses were used to estimate the risks of quartiles of E-DII score or depression on mortality.

Results

A total of 27,447 participants were included; including 24,694 subjects without cancer and 2,753 cancer survivors. The E-DII score and depression were not distributed differently between the two groups. However, the E-DII scores were positively associated with within each group’s depression (all P trend < 0.001) and participants with higher E-DII scores had a higher risk of depression (subjects without cancer: ORQ4vsQ1: 2.17, 95% CI: 1.75–2.70; cancer survivors: ORQ4vsQ1: 1.78, 95% CI: 1.09–2.92). The median follow-up time were 87 person-months, a total of 1,701 (4.8%) and 570 (15.2%) all-cause deaths in subjects without cancer and cancer survivors were identified by the end of 2019. The highest E-DII scores quartile was associated with the highest risk of all-cause (HRQ4vsQ1: 1.90, 95% CI: 1.54–2.35) and cardiovascular disease (CVD) cause death (HRQ4vsQ1: 2.50, 95% CI: 1.69–2.3.7) in the subjects without cancer. Moreover, participants with depressive symptoms had higher all-cause mortality (HR: 1.29, 95% CI: 1.04–1.59). No significant correlation was found for E-DII scores or depression with all-cause, cancer-cause or CVD-cause mortality in cancer survivors.

Conclusion

Our findings demonstrate that E-DII score was positively associated with depression risk. A higher E-DII score or depressive symptom may increase the risks of all-cause and CVD-cause mortality only among general subjects.
Chili pepper preference development and its impact on dietary intake: A narrative review
Authors: Siebert Emily , Lee Soo-Yeun , Prescott Melissa Pflugh
Published: December 2022

A preference for chili pepper can be an acquired taste. The contrast between a chili lover and a hater illustrates the complexities involved in forming an appreciation for food that evokes a fiery pain sensation. This narrative review aims to understand the factors behind chili pepper preference formation across the life course and how individual chili pepper preferences can impact eating behaviors and dietary intake. This review was conducted using three databases, yielding 38 included articles. Results suggest five determinants of chili pepper preferences: culture, exposure, gender, genetics, and personality. Collective findings indicate that the strongest influences on preference acquisition include the individual environment from childhood to adulthood and repeated exposure to spicy flavors. With frequent exposure to spicy food, the perceived burn becomes less intense. Culture also influences exposure to chili peppers, with the highest consumption patterns seen within Mexico and some Asia countries. Additionally, males reported having a stronger preference for spicy foods than females. Twin studies illustrated that genetics influenced spicy taste preferences, underscoring the complexity of developing individual taste preferences. As for the impact of capsaicin-containing food on individual eating behaviors and dietary behaviors, appetite effects depend on the dose of capsaicin consumed, but three studies found a change in sensory desires for sweet and fatty foods after finishing a capsaicin-containing dish. Inconsistent results were reported for chili pepper's effects on hunger and satiety after consumption, but changes in specific food desires were observed. The impact of chili pepper on appetite and calories consumed was inconsistent, but the greater amount of capsaicin ingested, the greater the effect. Capsaicin's potential to be used for weight control needs to be further reviewed. In conclusion, evidence suggests that chili pepper preferences may be linked to innate and environmental aspects such as an individual's culture, gender, and genetics. Extrinsic factors like repeated exposure may increase the liking for spicy foods.
Antioxidant capacity, phytochemical profiles, and phenolic metabolomics of selected edible seeds and their sprouts
Authors: Liu Hong-Yan , Liu Yi , Li Ming-Yue , Ge Ying-Ying , Geng Fang , He Xiao-Qin , Xia Yu , Guo Bo-Li , Gan Ren-You
Published: December 2022

Sprouts are recognized as nutritional and functional vegetables. In this study, 17 selected seeds were germinated simultaneously. The antioxidant capacity and total phenolic content (TPC) were determined for seeds and sprouts of all species. Both seed and sprout of white radish, with the highest antioxidant capacity, and TPC among all the 17 species, were further determined for phenolic metabolomics. Four phenolic classes with 316 phenolic metabolites were identified. 198 significantly different metabolites with 146 up-regulated and 52 down-regulated were confirmed, and high amounts of phenolic acids and flavonoids were found to be accumulated in the sprout. Several metabolism and biosynthesis, including phenylpropanoid, favone and flavonol, phenylalanine, and various secondary metabolites, were significantly activated. Significant correlations were found among FRAP, DPPH, ABTS, TPC, and phenolic profiles. Therefore, white radish sprout could be served as antioxidant and could be a good source of dietary polyphenols.
Relationship between nutritional status and length of hospital stay among patients with atrial fibrillation – a result of the nutritional status heart study
Authors: Czapla Michał , Uchmanowicz Izabella , Juárez-Vela Raúl , Durante Angela , Kałużna-Oleksy Marta , Łokieć Katarzyna , Baeza-Trinidad Ramón , Smereka Jacek
Published: December 2022

Background

Nutritional status is related to the prognosis and length of hospital stay (LOHS) of patients with atrial fibrillation (AF). This study aimed to assess how nutritional status affects LOHS for patients with AF.

Methods

We performed retrospective analysis of the medical records of 1,813 patients admitted urgently with a diagnosis of AF to the Institute of Heart Diseases of the University Clinical Hospital in Wroclaw, Poland.

Results

In total, 1,813 patients were included in the analysis. The average LOHS in the entire group was 3.53 ± 3.41 days. The mean BMI was 28.7 kg/m2 (SD: 5.02). Patients who were hospitalized longer were statistically more likely to have a Nutritional Risk Score (NRS) ≥3 (p = 0.028). A higher percentage of longer hospitalized patients with LDL levels below 70 mg/dl (p < 0.001) and those with HDL ≥40 mg/dl (p < 0.001) were observed. Study participants with NRS ≥3 were an older group (M = 76.3 years), with longer mean LOHS (M = 4.44 days). The predictors of LOHS in the univariate model were age (OR = 1.04), LDL (OR = 0.99), HDL (OR = 0.98), TC (OR = 0.996), CRP (OR = 1, 02, p < 0.001), lymphocytes (OR = 0.97, p = 0.008) and in the multivariate model were age, LDL (mg/dl), HDL (mg/dl), Na, and K.

Conclusion

For nutritional status, factors indicating the risk of prolonged hospitalization in patients with AF are malnutrition, lower serum LDL, HDL, potassium, and sodium levels identified at the time of admission to the cardiology department. Assessment of nutritional status in patients with AF is important both in the context of evaluating obesity and malnutrition status, as both conditions can alter the prognosis of patients. Further studies are needed to determine the exact impact of the above on the risk of prolonged hospitalization.
Development and validation of prognostic nomograms in patients with gallbladder mucinous adenocarcinoma: A population-based study
Authors: Xu Xiaoming , Wang Jingzhi
Published: December 2022

Background

Gallbladder mucinous adenocarcinoma (GBMAC) is an uncommon malignant gallbladder tumor. There are few studies on its prognosis, with the majority consisting of small series or individual cases. We sought to develop and validate nomograms for predicting overall survival (OS) and cancer-specific survival (CSS) in GBMAC patients.

Methods

The clinicopathological data of GBMAC patients from 1975 to 2019 was extracted from the Surveillance, Epidemiology, and End Results (SEER) database, and all patients were randomly divided into a training cohort (70%) and a validation cohort (30%). Using multivariate Cox regression analyses based on Akaike information criterion (AIC), prognostic and important variables for GBMAC were determined. On the basis of these factors, nomograms were developed to predict the 1-, 3-, and 5-year OS and CSS rates of patients with GBMAC. Multiple parameters, including the area under the subject operating characteristic curve (AUC), the calibration plots, and the decision curve analysis (DCA), were then used to evaluate the accuracy of nomograms.

Results

Following exclusion, a total of 707 GBMAC patients were enrolled, and the training cohort (490, 70%) and validation cohort (217, 30%) were randomly assigned. Grade, surgery, radiation, and SEER stage were predictive factors for patients with GBMAC, as indicated by univariate and multivariate Cox regression analyses based on AIC. We created nomograms for predicting OS and CSS in GBMAC using the four factors. The calibration curves and area under the curves (AUCs) indicated that our nomograms have a moderate degree of predictive accuracy and capability. The results of the DCA revealed that the nomogram has a high predictive value.

Conclusion

We established the first nomograms for predicting 1-, 3-, and 5-year OS and CSS in GBMAC patients, thereby contributing to the prognostication of patients and clinical management.
Physiologically based pharmacokinetic modelling and simulation to predict the plasma concentration profile of schaftoside after oral administration of total flavonoids of Desmodium styracifolium
Authors: Li Xue , Chen Chao , Ding Nan , Zhang Tianjiao , Zheng Peiyong , Yang Ming
Published: December 2022

Introduction: The total flavonoids of Desmodium styracifolium (TFDS) are the flavonoid extracts purified from Desmodii Styracifolii Herba. The capsule of TFDS was approved for the treatment of urolithiasis by NMPA in 2022. Schaftoside is the representative compound of TFDS that possesses antilithic and antioxidant effects. The aim of this study was to develop a physiologically based pharmacokinetic (PBPK) model of schaftoside to simulate its plasma concentration profile in rat and human after oral administration of the total flavonoids of Desmodium styracifolium.

Methods: The physiologically based pharmacokinetic model of schaftoside was firstly developed and verified by the pharmacokinetic data in rats following intravenous injection and oral administration of the total flavonoids of Desmodium styracifolium. Then the PBPK model was extrapolated to human with PK-Sim® software. In order to assess the accuracy of the extrapolation, a preliminary multiple-dose clinical study was performed in four healthy volunteers aged 18–45 years old. The predictive performance of PBPK model was mainly evaluated by visual predictive checks and fold error of Cmax and AUC0-t of schaftoside (the ratio of predicted to observed). Finally, the adult PBPK model was scaled to several subpopulations including elderly and renally impaired patients.

Results: Schaftoside underwent poor metabolism in rat and human liver microsomes in vitro, and in vivo it was extensively excreted into urine and bile as an unchanged form. By utilizing literature and experimental data, the PBPK model of schaftoside was well established in rat and human. The predicted plasma concentration profiles of schaftoside were consistent with the corresponding observed data, and the fold error values were within the 2-fold acceptance criterion. No significant pharmacokinetic differences were observed after extrapolation from adult (18–40 years old) to elderly populations (71–80 years) in PK-Sim®. However, the plasma concentration of schaftoside was predicted to be much higher in renally impaired patients. The maximum steady-state plasma concentrations in patients with chronic kidney disease stage 3, 4 and 5 were 3.41, 12.32 and 23.77 times higher, respectively, than those in healthy people.

Conclusion: The established PBPK model of schaftoside provided useful insight for dose selection of the total flavonoids of Desmodium styracifolium in different populations. This study provided a feasible way for the assessment of efficacy and safety of herbal medicines.
Achieving relativistically intense X-rays from structured plasma lens
Authors: Chen Peng , Huang Taiwu , Jiang Ke , Yu Mingyang , Zhou Cangtao
Published: December 2022

Focusing of high-power X-rays is still a great challenge and the intensity of X-ray attained in existing focusing schemes is still far below the relativistic threshold. Here, we propose that solid density plasma lens can potentially focus X-ray lasers at very high power levels. The interaction of high-power X-ray laser with solid-density plasmas is systematically studied. It is theoretically shown that there exists a certain range of wavelengths for X-ray lasers that can be focused in solid-density plasmas when the input power and plasma density are determined. To avoid the essential laser-plasma instabilities and obtain high-gain intensity amplification for X-ray, we design concave structured plasma lens. Particle-in-cell simulation results show that such regime can effectively avoid the instabilities and focus X-ray of micrometer-sized spot and multi-TW power, and thus lead to the generation of relativistic intensity X-ray. The parameters of the concave structures and the effects of quantum electrodynamics are also discussed and it indicates that our scheme is quite robust. We further demonstrate that the relativistic X-ray laser interacting with thin-foil leads to high-quality attosecond electron bunches.
Comprehensive molecular and morphological resolution of blubber stratification in a deep-diving, fasting-adapted seal
Authors: Khudyakov J. I. , Allen K. N. , Crocker D. E. , Trost N. S. , Roberts A. H. , Pirard L. , Debier C. , Piotrowski E. R. , Vázquez-Medina J. P.
Published: December 2022

Blubber is a modified subcutaneous adipose tissue in marine mammals that provides energy storage, thermoregulation, hydrodynamic locomotion, and buoyancy. Blubber displays vertical stratification by lipid content, fatty acid composition, and vascularization, leading to the assumption that deeper blubber layers are metabolically active, while superficial layers are mainly structural and thermoregulatory. However, few studies have examined functional stratification of marine mammal blubber directly, especially in pinnipeds. We characterized morphological and transcriptional differences across blubber layers in the northern elephant seal, a deep-diving and fasting-adapted phocid. We collected blubber from seals early in their fasting period and divided blubber cores into three similarly sized portions. We hypothesized that the innermost blubber portion would have higher 1) heterogeneity in adipocyte size, 2) microvascular density, and 3) expression of genes associated with metabolism and hormone signaling than outer blubber. We found that adipocyte area and variance increased from outermost (skin-adjacent) to innermost (muscle-adjacent) blubber layers, suggesting that inner blubber has a higher capacity for lipid storage and turnover than outer blubber. Inner blubber had a higher proportion of CD144+ endothelial cells, suggesting higher microvascular density. In contrast, outer blubber had a higher proportion of CD4+ immune cells than inner blubber, suggesting higher capacity for response to tissue injury. Transcriptome analysis identified 61 genes that were differentially expressed between inner and outer blubber layers, many of which have not been studied previously in marine mammals. Based on known functions of these genes in other mammals, we suggest that inner blubber has potentially higher 1) adipogenic capacity, 2) cellular diversity, and 3) metabolic and neuroendocrine signaling activity, while outer blubber may have higher 1) extracellular matrix synthesis activity and 2) responsiveness to pathogens and cell stressors. We further characterized expression of nine genes of interest identified by transcriptomics and two adipokines with higher precision across blubber layers using targeted assays. Our study provides functional insights into stratification of blubber in marine mammals and a molecular key, including CD144, CD4, HMGCS2, GABRG2, HCAR2, and COL1A2, for distinguishing blubber layers for physiological and functional studies in seals.
qInward variability-based in-silico proarrhythmic risk assessment of drugs using deep learning model
Authors: Jeong Da Un , Qashri Mahardika T Nurul , Marcellinus Aroli , Lim Ki Moo
Published: December 2022

Many researchers have suggested evaluation methods and Torsades de Pointes (TdP) metrics to assess the proarrhythmic risk of a drug based on the in silico simulation, as part of the Comprehensive in-vitro Proarrhythmia Assay (CiPA) project. In the previous study, we validated the robustness of 12 in silico features using the ordinal logistic regression (OLR) model by comparing the classification performances of metrics according to the in-vitro experimental datasets used; however, the OLR model using 12 in silico features did not provide desirable results. This study proposed a convolutional neural network (CNN) model using the variability of promising in silico TdP metrics hypothesizing that the variability of in silico features based on beats has more information than the single value of in silico features. We performed the action potential (AP) simulation using a human ventricular myocyte model to calculate seven in silico features representing the electrophysiological cell states of drug effects over 1,000 beats: qNet, qInward, intracellular calcium duration at returning to 50% baseline (CaD50) and 90% baseline (CaD90), AP duration at 50% repolarization (APD50) and 90% repolarization (APD90), and dVm/dtMax_repol. The proposed CNN classifier was trained using 12 train drugs and tested using 16 test drugs among CiPA drugs. The torsadogenic risk of drugs was classified as high, intermediate, and low risks. We determined the CNN classifier by comparing the classification performance according to the variabilities of seven in silico biomarkers computed from the in silico drug simulation using the Chantest dataset. The proposed CNN classifier performed the best when using qInward variability to classify the TdP-risk drugs with 0.94 AUC for high risk and 0.93 AUC for low risk. In addition, the final CNN classifier was validated using the qInward variability obtained after merging three in-vitro datasets, but the model performance decreased to a moderate level of 0.75 and 0.78 AUC. These results suggest the need for the proposed CNN model to be trained and tested using various types of drugs.
An updated review on the link between oral infections and atherosclerotic cardiovascular disease with focus on phenomics
Authors: Bezamat Mariana
Published: December 2022

Atherosclerotic cardiovascular diseases (ACVD) and oral infections such as periodontal disease, dental caries, and apical periodontitis are diseases that affect a great portion of the worldwide population. Both are complex in nature and several studies show that they share etiological factors but a causal relationship between them has not been yet established due to the lack of well-designed clinical trials. Many studies in the recent years show convincing evidence of different mechanisms that might be involved in this association including chronic inflammation and immune response. However, some of these mechanisms are controversial because of confounding factors. It has been suggested that maladaptive inflammatory reactivity, determined in part by single nucleotide polymorphisms (SNPs) in pathway genes, could influence the association between oral infections, and cardiovascular diseases as pleiotropic genes. That is, these conditions could be outcomes of similar inflammatory pathways. Phenomics, the study of the changes in phenotypes or traits considering environmental variables and genetics is efficient in assessing and determining pleiotropic genes. Future research should focus on analyzing a combination of oral inflammatory conditions instead of focusing on one inflammatory phenotype alone and consider pleiotropy as a mechanistic contributor for these associations. Further, prospective observational studies seeking to follow the development of oral disease and subclinical ACVD will foster the understanding of the impact of oral health on general systemic health. Lastly, to demonstrate that oral infections would increase risk for subclinical ACVD development, clinical trials proposing to treat those infections considering genetic background and all other confounders are needed.
Piezo1-pannexin-1-P2X3 axis in odontoblasts and neurons mediates sensory transduction in dentinal sensitivity
Authors: Ohyama Sadao , Ouchi Takehito , Kimura Maki , Kurashima Ryuya , Yasumatsu Keiko , Nishida Daisuke , Hitomi Suzuro , Ubaidus Sobhan , Kuroda Hidetaka , Ito Shinichirou , Takano Masayuki , Ono Kentaro , Mizoguchi Toshihide , Katakura Akira , Shibukawa Yoshiyuki
Published: December 2022

According to the “hydrodynamic theory,” dentinal pain or sensitivity is caused by dentinal fluid movement following the application of various stimuli to the dentin surface. Recent convergent evidence in Vitro has shown that plasma membrane deformation, mimicking dentinal fluid movement, activates mechanosensitive transient receptor potential (TRP)/Piezo channels in odontoblasts, with the Ca2+ signal eliciting the release of ATP from pannexin-1 (PANX-1). The released ATP activates the P2X3 receptor, which generates and propagates action potentials in the intradental Aδ afferent neurons. Thus, odontoblasts act as sensory receptor cells, and odontoblast-neuron signal communication established by the TRP/Piezo channel-PANX-1-P2X3 receptor complex may describe the mechanism of the sensory transduction sequence for dentinal sensitivity. To determine whether odontoblast-neuron communication and odontoblasts acting as sensory receptors are essential for generating dentinal pain, we evaluated nociceptive scores by analyzing behaviors evoked by dentinal sensitivity in conscious Wistar rats and Cre-mediated transgenic mouse models. In the dentin-exposed group, treatment with a bonding agent on the dentin surface, as well as systemic administration of A-317491 (P2X3 receptor antagonist), mefloquine and 10PANX (non-selective and selective PANX-1 antagonists), GsMTx-4 (selective Piezo1 channel antagonist), and HC-030031 (selective TRPA1 channel antagonist), but not HC-070 (selective TRPC5 channel antagonist), significantly reduced nociceptive scores following cold water (0.1 ml) stimulation of the exposed dentin surface of the incisors compared to the scores of rats without local or systemic treatment. When we applied cold water stimulation to the exposed dentin surface of the lower first molar, nociceptive scores in the rats with systemic administration of A-317491, 10PANX, and GsMTx-4 were significantly reduced compared to those in the rats without systemic treatment. Dentin-exposed mice, with somatic odontoblast-specific depletion, also showed significant reduction in the nociceptive scores compared to those of Cre-mediated transgenic mice, which did not show any type of cell deletion, including odontoblasts. In the odontoblast-eliminated mice, P2X3 receptor-positive A-neurons were morphologically intact. These results indicate that neurotransmission between odontoblasts and neurons mediated by the Piezo1/TRPA1-pannexin-1-P2X3 receptor axis is necessary for the development of dentinal pain. In addition, odontoblasts are necessary for sensory transduction to generate dentinal sensitivity as mechanosensory receptor cells.
Homology-based identification of candidate genes for male sterility editing in upland cotton (Gossypium hirsutum L.)
Authors: Morales Karina Y. , Bridgeland Aya H. , Hake Kater D. , Udall Joshua A. , Thomson Michael J. , Yu John Z.
Published: December 2022

Upland cotton (Gossypium hirsutum L.) accounts for more than 90% of the world’s cotton production, providing natural material for the textile and oilseed industries worldwide. One strategy for improving upland cotton yields is through increased adoption of hybrids; however, emasculation of cotton flowers is incredibly time-consuming and genetic sources of cotton male sterility are limited. Here we review the known biochemical modes of plant nuclear male sterility (NMS), often known as plant genetic male sterility (GMS), and characterized them into four groups: transcriptional regulation, splicing, fatty acid transport and processing, and sugar transport and processing. We have explored protein sequence homology from 30 GMS genes of three monocots (maize, rice, and wheat) and three dicots (Arabidopsis, soybean, and tomato). We have analyzed evolutionary relationships between monocot and dicot GMS genes to describe the relative similarity and relatedness of these genes identified. Five were lowly conserved to their source species, four unique to monocots, five unique to dicots, 14 highly conserved among all species, and two in the other category. Using this source, we have identified 23 potential candidate genes within the upland cotton genome for the development of new male sterile germplasm to be used in hybrid cotton breeding. Combining homology-based studies with genome editing may allow for the discovery and validation of GMS genes that previously had no diversity observed in cotton and may allow for development of a desirable male sterile mutant to be used in hybrid cotton production.
Caffeoyl-CoA 3-O-methyltransferase gene family in jute: Genome-wide identification, evolutionary progression and transcript profiling under different quandaries
Authors: Akhter Saima , Sami Asif Ahmed , Toma Tamanna Islam , Jahan Bushrat , Islam Tahmina
Published: December 2022

Jute (Corchorus sp.), is a versatile, naturally occurring, biodegradable material that holds the promising possibility of diminishing the extensive use of plastic bags. One of the major components of the cell wall, lignin plays both positive and negative roles in fiber fineness and quality. Although it gives mechanical strength to plants, an excess amount of it is responsible for the diminution of fiber quality. Among various gene families involved in the lignin biosynthesis, Caffeoyl-CoA 3-O-methyltransferase (CCoAOMT) is the most significant and has remained mostly unexplored. In this study, an extensive in-silico characterization of the CCoAOMT gene family was carried out in two jute species (C. capsularis L. and C. olitoroius L.) by analyzing their structural, functional, molecular and evolutionary characteristics. A total of 6 CCoAOMT gene members were identified in each of the two species using published reference genomes. These two jute species showed high syntenic conservation and the identified CCoAOMT genes formed four clusters in the phylogenetic tree. Histochemical assay of lignin in both jute species could shed light on the deposition pattern in stems and how it changes in response to abiotic stresses. Furthermore, expression profiling using qPCR showed considerable alteration of CCoAOMT transcripts under various abiotic stresses and hormonal treatment. This study will lay a base for further analysis and exploration of target candidates for overexpression of gene silencing using modern biotechnological techniques to enhance the quality of this economically important fiber crop.
Analysis of desertification combating needs based on potential vegetation NDVI—A case in the Hotan Oasis
Authors: Zhang Lei , Qu Jia , Gui Dongwei , Liu Qi , Ahmed Zeeshan , Liu Yi , Qi Zhiming
Published: December 2022

Combating desertification is vital for arresting land degradation and ensuring sustainable development of the global ecological environment. This study has analyzed the current desertification status and determined its control needs based on the difference between potential normalized difference vegetation index (PNDVI) and actual normalized difference vegetation index (ANDVI) in the Hotan desertoasis. The MaxEnt model, combined with the distribution point data of natural vegetation with long-term stable normalized difference vegetation index (NDVI) and 24 environmental factors was used to predict the PNDVI spatial distribution of different vegetation coverage grades and compared it with ANDVI. Excluding the areas of intense human activity such as arable land, the simulation results show that PNDVI with high, medium, and low vegetation cover was mainly distributed in the southwest and southeast of Hotan Oasis, in the midstream and downstream of Kalakash River and Yulong Kashi River, and the desert or Gobi area outside the oasis, respectively. The distribution of PNDVI with high, medium, and low vegetation cover accounted for 6.80%, 7.26%, and 9.17% of Hotan oasis, respectively. The comparison between ANDVI and PNDVI shows that 18.04% (ANDVI < PNDVI, about 3900 km2) of the study area is still suffering from desertification, which is mainly distributed in the desert-oasis ecotone in Hotan. The findings of this study implied that PNDVI could be used to assess the desertification status and endorsement of desertification control measures in vulnerable ecosystems. Hence, PNDVI can strengthen the desertification combating efforts at regional and global scales and may serve as a reference point for the policymakers and scientific community towards sustainable land development.