bluuebunny/crossref_metadata_2025 huggingface dataset:
Electronic origin of ultrafast laser-induced ferroelectricity in SrTiO3
Authors: Zhang Cui , Song Chenchen , Yang Qing , Liu Xinbao , Zhao Hui , Meng Sheng
Published: June 2022

Following an ultrafast laser excitation, paraelectric SrTiO3 can be driven non-thermally into a metastable ferroelectricity state. Despite achieving ultrafast control of ferroelectricity, the fundamental mechanism and dynamics of the photoinduced phase transition remain ambiguous. Here, the determinant formation mechanism of ultrafast ferroelectricity in SrTiO3 is traced by non-adiabatic dynamics simulations. That is, the selective excitation of multiple phonons, induced by photoexcited electrons through the strong correlation between electronic excitation and lattice distortion, result in the breaking of the crystal central symmetry and the onset of ferroelectricity on the ultrafast time scale. Laser illumination leads to a uniaxially stretched lattice deformation along the laser polarization direction, generated by nonequilibrium forces from optically excited electrons. The accompanying population transition between 3dz2 and 3d(x2-y2) orbitals excites multiple phonon branches, including the two high-energy longitudinal optical modes, so as to drive titanium ion away from the center of oxygen octahedron and generate a metastable ferroelectric phase. These findings provide new insights into the understanding and manipulation of laser-induced ferroelectric phase transition, and suggests new schemes for the optical control of electronic and structural quantum states in complex materials.
Integrated Metabolomics and Transcriptomics Analyses Reveal Anthocyanin and Carotenoid Biosynthesis Involved in Color Development in Willow Bark
Authors: Zhou Jie , Guo Jiahui , Chen Qingsheng , Wang Baosong , He Xudong , Zhuge Qiang , Wang Pu
Published: June 2022

Background The rich yellow-orange to vividly deep red bark of willow (Salix spp.) branches have great ornamental and economic value. The mechanism of willow branch color has not been clarified yet. ResultsTo study the mechanisms regulating color development, we performed metabolomics and transcriptomics analyses using purple, green, and red willow barks. Seven anthocyanins were isolated; pelargonidin, petunidin 3-O-rutinoside, and cyanin chloride were the most abundant in the red bark and pelargonin chloride in the purple bark. Among the barks, green bark had the highest level of malvidin, but its level was not significantly higher than in the red bark; the purple bark had the highest amount of canthaxanthin, a carotenoid pigment. The integrated biosynthetic pathway of flavonoid, carotenoid, and chlorophyll was constructed for willow barks. Among the three barks, the expression of the structural genes ANS, ANR, and BZ1, involved in anthocyanin synthesis, was highest in the red bark, likely causing anthocyanin accumulation. The highest expression of CrtZ, involved in the carotenoid pathway, was observed in the purple bark, likely causing canthaxanthin accumulation. The high expression of DVR, POR, and CRD1 may be associated with the green pigment synthesis in chlorophyll biosynthetic pathway. Our research findings will facilitate genetic breeding to improve the color and luster of willows. ConclusionsIn conclusion, the purple bark is co-regulated by anthocyanins and carotenoids. The red bark is characterized by anthocyanin accumulation and chlorophyll degradation. The green pigment is regulated by maintaining of chlorophyll synthesis. The key regulation genes BZ1, CrtZ could be candidate genes regulating anthocyanin and canthaxanthin accumulation in red and purple barks. Our research findings facilitate the genetic breeding and cultivation of colorful willows with improved color and luster.
Pulmonary Function Changes After Sublobar Resection In Patients With Peripheral Non-Subpleural Nodules
Authors: Feng Kun-Peng , Shen Zi-Qing , Xu Chun , Ding Cheng , Feng Yu , Zhu Xin-Yu , Pan Bin , Jia Xin-Yu , Zhao Jun , li Chang
Published: June 2022

Background: in the treatment of peripheral early-staged lung cancer and benign lesions, segmentectomy and wedge resection are both reliable treatment methods. It is debatable that how much pulmonary function will be lost after different sublobar resection in the treatment of early-staged deep-located peripheral NSCLC (non-small cell lung cancer). The purpose of this study was to explore postoperative pulmonary function changes of sublobar resection in enrolled patients with non-subpleural peripheral nodules. Methods: we collected clinical data of patients undergoing VATS (video-assisted thoracoscopic surgery) segmentectomy or wedge resection for single nodule. These nodules were confirmed as peripheral non-subpleural nodules by preoperative 3D imaging. Patients were divided into two groups according to the operation procedure. Demographic characteristics, pulmonary function, postoperative outcomes，and others were collected. All data was gathered at the First Affiliated Hospital of Soochow University. Outcomes after wedge resection were compared with those after segmentectomy resection. Results: A total of 88 patients were included in this study, including 46 patients with VATS wedge resection and 42 patients with VATS segmentectomy. No difference was detected when comparing FEV1 (Forced Expiratory Volume in One Second) loss between these two groups (17.6389±2.18267%, wedge resection vs. 19.401±5.42039%, segmentectomy, P=0.176). FVC (Forced Vital Capacity) loss (8.7922±2.36723%, wedge resection vs. 17.1267±2.26517%, segmentectomy, P<0.001) and MVV (Maximum Ventilatory Volume) loss (11.543±3.1547%, wedge resection vs. 20.639±7.8527%, segmentectomy, P<0.001) in segmentectomy group was significantly higher than those in wedge resection group. Discrepancies were investigated when comparing duration of surgery (70.43±22.615mins, wedge resection vs. 111.76±52.455mins, segmentectomy, P=0.0002), postoperative drainage (85.65±45.209mL, wedge resection vs. 287.62±672.115mL, segmentectomy, P=0.0123), and treatment hospitalization expenses [35148±889CNY, wedge resection vs. 52502(38276~57772) CNY, segmentectomy, P<0.0002]. No significant difference was found between air leak time (1.78±0.736days, wedge resection vs. 2.57±1.72days, segmentectomy, P=0.062) and hospitalization time (2.78±0.736days, wedge resection vs. 3.57±1.72days, segmentectomy, P=0.051). Conclusions: For patients with peripheral non-subpleural nodules, wedge resection did not cause more loss of lung function than segmental resection. Patients undergoing wedge resection had partial advantages over patients with segmental resection in terms of hospitalization cost, operation time and postoperative drainage, etc. Wedge resection, as a treatment for peripheral non-subpleural pulmonary nodules, had no worse outcome than segmentectomy.
Understanding the Rain-shelter and Water and Fertilizer Management in Reducing Root rot of Panax notoginseng
Authors: Zhang Yan , Zang Zhennan , Tang Zhenya , Yang Qiliang
Published: June 2022

Purpose Panax notoginseng (Burk) F. H. Chen, a valuable Chinese medicinal herb,is widely used in chinese medicine products. The frequent root-rot, however, caused a large reduction of Panax notoginseng yields, which greatly affected the development of Panax notoginseng planting. Panax notoginseng root-rot is related to its warm and humid growing environment.Methods Thus, five-year-old Panax ginseng was selected to investigate the effects of water and fertilizer conditions in rain-sheltered and non-rain-sheltered environments on the incidence of Panax ginseng root-rot disease in field trials. Two irrigation (W1: 50% of field water holding capacity, W2: 70% field water holding capacity), and four fertilizer amounts (F0:0 kg ha-1, F1:75 kg ha-1, F2:105 kg ha-1, and F3:135 kg ha-1) were chosed in rain-sheltered and non-rain-sheltered, respectively.Results The results showed that water and fertilizer coupling under rain-sheltered or non-rain-sheltered conditions had significant effects on Panax notoginseng root-rot disease as well as agronomic traits. Compared with non-rain shelter cultivation, the rain-shelter treatments led to higher net photosynthetic rate, and root volume of Panax notoginseng, and promoted the soil respiration and soil enzyme activity, as well as decreased the soil moisture. Additionally, The incidence of root-rot in 50% irrigation level non-rain shelter treatment (RWF) were 52.97% -88.46% higher than that in corresponding 50% rain shelter treatment (P<0.05), and 97.80% -137.30% in 70% irrigation level. F2 fertilizer led to the lowest root-rot in rain-shelter treated Panax notoginseng, and F1 in non-rain-shelter treated Panax notoginseng. Structural equation modeling showed soil moisture was the main factor affecting root-rot with contribution of 0.545.Conclusions Comprehensive analysis of detected parameter of plant and soil, the DW2F2 was recommended with higher root valume and lower root-rot than the other treatments.
Anatomical basis for the trigeminal autonomic cephalalgia-like response produced by formalin injection into the facial cheek in rats
Authors: Wang Ming R , Tseng Ching J , Kuo Jon S
Published: June 2022

Trigeminal autonomic cephalalgias (TACs) comprise cluster headaches and are characterized by unilateral neuralgiform headache attacks associated with autonomic responses and somatic responses. An animal model for evaluating the anatomical basis of the TAC-like response is not currently available. Twenty-five rats weighing 550-650 g were anaesthetized with urethane. The TAC-like response was produced either by subcutaneous injection of formalin into the unilateral facial cheek or by electrical stimulation of the unilateral intact trigeminal nerve. The induced TAC-like response, which included ipsilateral common carotid arterial flow (iCCAF) and other autonomic responses, was studied in intact nerves or after cutting either the ipsilateral trigeminal nerve or the ipsilateral facial nerve. The formalin injections produced concentration-dependent iCCAF increases accompanied by ipsilateral autonomic responses of rhinitis-like nasal congestion, nasal mucus, meiosis, lacrimation, red eye, and eyelid oedema. The formalin (5% or 10%, 0.5 cc)-induced responses were nearly abolished by sectioning of either the facial or trigeminal nerve. The electrical stimulation (15 V, 60 Hz, and 0.4 ms) of the intact trigeminal nerve or its ophthalmo-maxillary branch also produced stimulation strength-dependent iCCAF increases as well as autonomic responses; however, the electrical stimulation-induced iCCAF increases and other autonomic responses could still be induced by electrical stimulation of the central but not the peripheral end of the ophthalmo-maxillary branch (n = 8) or the trigeminal nerve (n = 2). Thus, an animal model for inducing the TAC-like response by subcutaneous formalin injection into the rat facial cheek was established. The TAC-like response could be sequentially mediated via the afferent trigeminal nerve, trigeminal nucleus, dorsal facial nucleus, and efferent facial nerve.
KBTBD11, encoding a novel PPARγ target gene, is involved in NFATc1 proteolysis by interacting with HSC70 and HSP60
Authors: Watanabe Kazuhisa , Matsumoto Ayumi , Tsuda Hidetoshi , Iwamoto Sadahiko
Published: June 2022

We previously revealed that Kbtbd11 mRNA levels increase during 3T3-L1 differentiation and Kbtbd11 knockdown suppresses whereas its overexpression promotes adipogenesis. However, how Kbtbd11 mRNA is regulated during adipocyte differentiation and how the KBTBD11 protein functions in adipocytes remain elusive. This study aimed to examine the transcriptional regulatory mechanism of Kbtbd11 during adipocyte differentiation, KBTBD11-interacting protein functions, and elucidate the role of KBTBD11 in adipocytes. First, we identified the PPRE consensus sequences in the Kbtbd11 exon 1- and intron 1-containing region and demonstrated that PPARγ acts on this region to regulate Kbtbd11 expression. Next, we purified the KBTBD11 protein complex from 3T3-L1 adipocytes and identified heat shock proteins HSC70 and HSP60 as novel KBTBD11-interacting proteins. HSC70 and HSP60 inhibition increased KBTBD11 protein levels that promoted NFATc1 ubiquitination. These data suggested that HSC70 and HSP60 are involved in KBTBD11 stabilization and are responsible for NFATc1 regulation on the protein level. In summary, this study describes first the protein regulatory mechanism of NFATc1 through the HSC70/HSP60-KBTBD11 interaction that could provide a potential new target for the differentiation and proliferation of various cells, including adipocytes and tumors.
Gut microbiota from patients with mild COVID-19 cause alterations in mice that resemble post-COVID syndrome
Authors: de Almeida Viviani Mendes , Engel Daiane F , Ricci Mayra Fernanda , Cruz Clênio Silva , Lopes Icaro Santos , Alves Daniele Almeida , Auriol Mirna d’ , Magalhães João , Zuccoli Giuliana S. , Smith Bradley Joseph , Carregari Victor Corasolla , Machado Elayne Cristina , Rocha Victor M. , Carvalho Toniana G. , Lacerda Larisse de Souza Barbosa , Pimenta Jordane C. , Galvão Izabela , Silva Mariana Aganetti , Rosa Erika da Silva , Cassali Geovanni Dantas , Garcia Cristiana C. , Teixeira Mauro Martins , Coelho Leiliane , Ribeiro Fabiola Mara , Martins Flaviano S. , Saia Rafael Simone , Costa Vivian Vasconcelos , Martins-de-Souza Daniel , Marques João T. , Aguiar Eric R. G. R. , Vieira Angelica T.
Published: June 2022

Background
There is mounting evidence that SARS-CoV-2 targets tissues beyond the respiratory tract. Long-term sequelae after COVID-19 are frequent and of major concern. Prolonged virus detection in the gut has been particularly intriguing. Of note, SARS-CoV-2 infection also disturbs the gut microbiota composition, a finding linked with disease severity in patients with COVID-19. Here, we aimed to characterize the functional role of the gut microbiota in the long-term consequences of COVID-19. To this end, we characterized the gut microbiota from COVID-19 human subjects and followed the effects of human fecal transfer to germ-free mice.
Results
The gut microbiota of post-COVID subjects (up to 4 months from the initial positive test) revealed a remarkable predominance of Enterobacteriaceae strains with multidrug-resistance phenotype compared to healthy controls. After fecal transfer to germ-free mice, animals receiving samples from post-COVID subjects displayed higher lung inflammation and increased susceptibility to pulmonary infection caused by an antimicrobial resistant Klebsiella pneumoniae strain. These mice also showed poorer cognitive performance associated with increased expression of TNF-α, reduced levels of brain-derived neurotrophic factor-BDNF and postsynaptic density protein-PSD-95 in the brain, as well as alterations of several biochemical pathways. These alterations were observed in the absence of SARS-CoV-2, suggesting that alterations in the gut microbiota caused them. Consistent with this hypothesis, brain dysfunctions induced in a mouse model of coronavirus infection were partially prevented by modulation of the microbiota via treatment with the commensal probiotic bacteria Bifidobacterium longum 51A.
Conclusions
Our results show prolonged impact of SARS-CoV-2 infection in the gut microbiota that persists even after the individuals have cleared the virus. Increased Enterobacteriaceae with antimicrobial resistance phenotype were of particular concern. Moreover, microbiota transfer from post-COVID subjects induced loss of brain cognitive functions and impaired lung defense in mice. Altogether, our work emphasizes the importance of microbiota as a target for therapies to help treat post-COVID sequelae.
EGR1 mediating EP300 upregulation to alleviate Pulmonary arterial hypertension
Authors: YANG Lei , WANG Jun , CHEN Jidong , WANG Ting , LIN Boya , LINNEMAN John , L Li , NIU Yanqin , Gou Deming
Published: June 2022

Background
pulmonary arterial hypertension (PAH) is a lethal disease characterized by pulmonary vascular remodeling, which is mediated by the abnormal proliferation/migration of pulmonary arterial smooth muscle cells (PASMCs). Recent reports suggest the involvement of histone acetylation in PAH development and that histone deacetylase (HDAC) inhibitors have therapeutic potential for PAH. EP300 is an acetyltransferase that plays diverse roles in cell proliferation, differentiation, and apoptosis. However, little is known about its function in relation to PAH.
Results
in this work, we found that the expression of EP300 was found to be increased in the pulmonary arteries of Monocrotaline (MCT)-induced PAH rat models. EP300-knockdown exacerbated the MCT-induced PAH rats, with a higher right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI), and wall thickness in the pulmonary artery. On a cellular level, the proliferation of PASMCs was promoted by EP300 knockdown. In addition, the expression of EP300 was increased by the overexpression of EGR1 in PASMCs, while the deletion of EGR1 binding sites in the EP300 promoter region decreased the activity of the EP300 promoter. Moreover, deleting the EP300 promoter region containing EGR1 binding sites using CRISPR/Cas9 abolished the upregulation of EP300 in MCT-induced rats and exacerbated MCT-induced PAH. To summarize, our data indicates that EP300 upregulation mediated by EGR1 has a protective effect in MCT-induced PAH.
Conclusions
this work is the first report to find that EP300 expression is increased in MCT-induced PAH mediated by EGR1, and EP300 has potential to provide protection from PAH.
Evaluation of the coracoid bone tunnel placement on Dog Bone button fixation for acromioclavicular joint dislocation: a cadaver study combined with finite element analysis
Authors: Gao Rangshan , Zhang Wendong , Yang Yuxia , Zhang Yucheng , Hu Yangyang , Wu Honghai , Liu Mingsheng , Fei Wenyong , Wang Jingcheng
Published: June 2022

Background: Dog Bone button fixation was frequently used to treat acromioclavicular joint (ACJ) dislocation. However, there were many studies reporting about complications after fixation.Objective: To investigate the effect the coracoid bone tunnel location had on the treatment of ACJ dislocation using a single‑tunnel coracoclavicular (CC) ligaments fixation with the Dog Bone button.Methods: Six cadaveric shoulders were used. Each specimen underwent five testing conditions, performed in the following order: (1) normal ACJ (Gn). (2) The acromioclavicular and CC ligaments were removed (G0). (3) The CC ligament reconstruction was performed using the Dog Bone technique and the coracoid bone tunnel was at the center of the coracoid base (G1), or (4) 5 mm distal from the G1 site, along the axis of the coracoid (G2), or (5) 10 mm distal from the G1 site, along the axis of the coracoid (G3). The angles of pronation and supination of the clavicles under the same load (30 N) were measured. Next, a finite element (FE) model was created by using computed tomography (CT) images from the normal shoulder. Model 1 (M1), model 2 (M2), and model 3 (M3) correspond to G1, G2, and G3, respectively. A force of 70 N was used as a vertical upward load added to the distal clavicle. Consequently, the von Mises stress and the strain LE along the FiberWire and the displacement nephogram of the three models have been obtained.Results: After single-tunnel CC ligaments fixation using the Dog Bone technique, the clavicles in group G2 (20.50 (19.50, 21.25) °, 20.00 (18.75, 21.25) °) were the most stable (P < 0.001). The peak von Mises stress and the strain LE along the FiberWire, and the maximum displacement in M2 were all smaller than in M1 and M3.Conclusions: When the coracoid bone tunnel is located 5 mm anterior to the center of the coracoid base (along the axis of the coracoid), the clavicle gained greater stability.
Comparison of clinical characteristics of first-episode Thrombotic Thrombocytopenic Purpura and TTP-like syndrome: a retrospective cohort study in a level I hematology centre in China
Authors: Dong Guiying , Gao Weibo , Shi Fang-e , Zhang Xiaohui , Zhu Jihong
Published: June 2022

Aims: Comparing the characteristics of thrombotic thrombocytopenic purpura (TTP) and TTP-like syndrome patients at admission to allow early differentiation of TTP from TTP-like syndrome and help tailor initial treatment.Methods: The medical records of 78 patients with suspected TTP in the emergency department of Peking University People’s Hospital in the past five years were retrospectively analyzed retrospectively and divided into TTP and TTP-like syndrome groups based on ADAMTS13 activity and ADAMTS13 antibody titer.Results: There were 25 and 53 patients in the TTP group and the TTP-like syndrome group, respectively. The PLASMIC score was significantly higher in the TTP group than in the TTP-like syndrome group (P=0.006). The TTP group were more susceptible to receiving plasma exchange and glucocorticoids (P<0.001), and also less vulnerable to the plasma infusion (P<0.001). The etiology induced by autoimmune disease was more prominent in the TTP group (P<0.001). The neutrophil-to-lymphocyte ratio (P=0.025) was tremendously higher, and albumin (P=0.002) was lower in the TTP-like syndrome group, indicating a more severe infection. Compared with the TTP-like syndrome group, the TTP group had an approximately two-fold to three-fold higher prevalence of central nervous system dysfunction (P<0.001). Also, hemolysis was more substantial in the TTP group as evidenced by higher schistocytes (P<0.001), reticulocyte (P<0.001), total bilirubin (P=0.002), indirect bilirubin (P<0.001), lactate dehydrogenase (P=0.007) and cell-free hemoglobin (P<0.001), simultaneously lower platelet (P<0.001), haptoglobin (P=0.044) and ADAMTS13 activity (P<0.001). The Kaplan–Meier survival analysis showed that the TTP group significantly predicted poor prognosis (log-rank test: X2 =5.368, P=0.021).Conclusion: TTP and TTP-like syndrome are two kinds of distinct phenotypes with different hemolysis statuses and illustrated differentiated inflammatory reactions, target organ damage (TOD), and their clinical outcome.
Apolipoprotein L1 Genetic Variants in Cameroonians with chronic kidney disease: A case control study
Authors: Krystel Kekay , Ambroise Wonkam , Martin Ekiti E. , Francois Kaze F. , Livo Esemu , Gloria Ashuntantang
Published: June 2022

Background: This study aimed at investigating the apolipoprotein L1 genetic variants in non-diabetic chronic kidney disease among Cameroonians.Methods: A total of 179 non-diabetic CKD (100 cases and 79 controls), matched for; age, sex and comorbidities were included and genotyped by real-time Polymerase Chain Reaction for the Apolipoprotein L1 risk variants at the Division of Human Genetics, University of Cape Town, South Africa and at the National Centre for Filariasis and other Tropical diseases in Yaounde, Cameroon. Cases were patients with a biological or biopsy-proven diagnosis of CKD whereas Controls were patients with a risk factor for CKD except for diabetes with a normal renal function.Results: Frequencies of the two risk alleles was twofold higher amongst cases (29%) compared to the controls (13.9%). The odds of having the two APOL 1 genetic variants (GI/G2) was 2,5folds in cases compared to controls (p=0.016; OR=2.53) in the recessive model of inheritance. The odds were even higher for the APOL1 G1 risk allele in the recessive model of inheritance (p = 0.007; OR 3.91).Conclusion: Apolipoprotein L1 genetic variants are common in the Cameroonians and may contribute to the susceptibility to non-diabetic chronic kidney in this population.
Effect of auricular acupoint acupressure stimulation on the pulmonary function of healthy adults: A randomized, crossover, double-blinded study
Authors: Bu Man-Yun , Ke Shi-Liang , Quan Ying-Chan , Li Hong , Li Yi-Ting , Yu Yi , Tang Zhi-Ming
Published: June 2022

BackgroundThe study aimed to investigate the effect of auricular acupoint acupressure stimulation of the auricular vagus nerve on pulmonary function.MethodsFifteen healthy subjects were enrolled in this randomized, crossover, double-blinded study. All subjects received real and sham stimulation conditions at intervals of more than 24 h. On the real stimulation condition, auricular acupoint sticking with Vaccaria seeds and continuous stimulation of acupressure was delivered on the auricular vagus nerve area., but no Vaccaria seeds and no acupressure were used for the sham stimulation condition. Tidal volume (VT), vital capacity (VC), maximal inspiratory pressure (MIP), and diaphragmatic excursions (DE) of normal and forced breathing were assessed before and after each stimulation condition.ResultsBefore stimulation, there were no significantly differences of VT, VC, MIP, and DE of normal breathing and forced breathing between real and sham conditions. After stimulation, the change rates of VT ( P = 0.005), VC(P = 0.021), MIP (P = 0.023), DE of normal breathing (P = 0.022) and DE of forced breathing (P < 0.001) was higher on the real condition.ConclusionsAuricular acupoint acupressure stimulation of the auricular vagus nerve can significantly improve pulmonary function, and its use should be promoted in clinical settings.Trial registrationThis study has been registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2200058836, Date of registration: 17/04/2022).
A novel REST-regulated lncRNA PCAT-NE1 induces neuroendocrine differentiation in castration-resistant prostate cancer
Authors: Chang Ching-Hsin , Yeh Wayne W. , Cheng Ting-Yu , Luo Yun-Li , Campbell Mel , Kuo Tse-Chun , Shen Tsai-Wen , Hong Yung-Chih , Tsai Cheng-Han , Peng Yu-Ching , Pan Chin-Chen , Yang Muh-Hwa , Shih Jean-Chen , Kung Hsing-Jien , Huang William J. , Chang Pei-Ching , Lin Tzu-Ping
Published: June 2022

Background Lineage plasticity is recognized as a treatment-induced resistance mechanism in prostate cancer (PCa) and contributes to the development of neuroendocrine prostate cancer (NEPC), a lethal variant of castration-resistant prostate cancer (CRPC), that is increasing in the era of second-generation anti-hormonal therapy. At present, there are no effective treatments for NEPC. Conclusions and perspectives Following our long-standing interest in studying RE1-silencing transcription factor (REST), a pivotal repressor of neuroendocrine differentiation (NED), we conducted a siRNA screening targeting 147 REST-repressing long non-coding RNAs (lncRNAs) and identified prostate cancer transcript-neuroendocrine 1 (PCAT-NE1) as a novel lncRNA that induces NED through activating autophagy signaling, crucial for NED of prostate adenocarcinoma cell. Analyses of clinical data and samples indicate that PCAT-NE1 is elevated in NEPC. Through gain- and loss-of-function experiments, we find that PCAT-NE1 promotes NED. Mechanistically, PCAT-NE1 acts as a competing endogenous RNA (ceRNA) that sponge hsa-miR-6889-3p, leading to the up-regulation of autophagy-related gene VPS13A and autophagy activation. These findings provide new insight into lncRNA-mediated mechanism for autophagy activation in NEPC and suggest PCAT-NE1 as a potential diagnostic biomarker and therapeutic target for NEPC.
Oral administration of an antiparasitic agent emamectin benzoate persuades dose-dependent histoarchitectural alterations in Nile tilapia Oreochromis niloticus (L.)
Authors: Abraham Thangapalam Jawahar , Julinta Roy Beryl , Patil Prasanna Kumar
Published: June 2022

A variety of drugs are administered orally to control parasitic diseases in aquaculture. This study assessed the effects of oral dose and dosage of an antiparasitic agent emamectin benzoate (EB) on the safety and kidney, liver, and intestine tissue histoarchitecture of Oreochromis niloticus. The EB-medication for 21 days at the recommended dose caused about 2% mortalities, 25% reduced feed intake, and 6.52% biomass reduction. The results revealed a dose-dependent hepatotoxic, nephrotoxic, and intestinal toxic potential of EB and the relationship between medication and the functioning of vital organs. Degeneration of the renal tubules and tubular epithelium, glomerulopathy, vacuolation, inflammation and necrotized renal interstitium were observed in the kidney. The liver tissues had glycogen-type vacuolation, cytoplasmic degeneration, and vacuolation. The intestine exhibited loss of absorptive vacuoles, mucinous degeneration, necrotized intestinal villi, inflammation, and necrotized absorptive region. Lamina propria swelling was noticed in the intestine of the higher dosed groups. With the termination of medication, the specific pathological changes were reduced significantly, indicating the ability of fish to mount adaptive responses to recoup. Though the EB at the recommended dose caused mortalities, reduced feed intake, and biomass during the extended EB-dosing as well as at the higher doses, it is unlikely to produce adverse and irrevocable effects on O. niloticus at the dose of 50 μg/kg biomass/day for 7 consecutive days. The inclusion of EB in the aquaculture medicine list for managing the external parasites would help boost the tropical freshwater fish health and production.
Diurnal Cycle of Precipitation Over Global Monsoon Systems in CMIP6 Simulations
Authors: Tao Cheng , Xie Shaocheng , Tang Shuaiqi , Lee Jiwoo , Ma Hsi-Yen , Zhang Chengzhu , Lin Wuyin
Published: June 2022

Accurate simulation of the diurnal cycle of precipitation over different climate regimes, including global monsoon systems, is an ongoing challenge for current state-of-the-art climate models. In this study, the diurnal cycles of summertime precipitation from 21 CMIP6 historical simulations are evaluated with the NASA IMERG data via the diurnal harmonic amplitude and phase from the Fourier analysis in seven regional monsoon systems: Northern and Southern Africa monsoons, South Asia monsoon, East Asia monsoon, Australia monsoon, and North and South America monsoons. Particularly, we focus on four subregions including ocean, coastal ocean, land, and coastal land considering the different underlying physical processes. It is found that the CMIP6 historical simulations perform fairly well on reproducing the diurnal cycle of precipitation over ocean and coastal ocean, while the simulated diurnal harmonic phase and amplitude over land and coastal land show larger biases and model spread compared to biases over ocean and coastal ocean. The simulation of precipitation diurnal cycle is substantially improved in the multi-model mean of both CMIP6 historical and CMIP6 AMIP simulations compared with that of CMIP5 historical simulations. But the model bias of precipitation diurnal cycle is in general similar between CMIP6 AMIP and CMIP6 historical simulations, which suggests that the impact of the interactive ocean on the simulated diurnal precipitation averaged over a large domain is generally minor. The influence of model resolution on the diurnal cycle is shown in mixed directions across various subregions, and significant improvement from the low- to high-resolution models is only notable over coastal ocean.
Effective Traffic Intensity of Prioritized IoT Networks with Packet Deadlines in Non-Preemptive M/M/1/2
Authors: Abdollahi Mehran Pourmohammad , Azarhava Hosein , Haghrah Amiraslan , Niya Javad Musevi
Published: June 2022

The intelligent traffic monitoring would be considered as one of the most important techniques to handle a great deal of data in Internet of Things (IoT) Networks. We consider an IoT network with three class of sensors which transmit their data to a Monitoring Center (MC). The MC with a great demand for fresh data, is equipped with one server and one buffer of capacity equal to one packet as a queueing model, representing an M/M/1/2 system. The characteristics of the group of devices, are specified with high, medium and low priorities, respectively. We consider a Rayleigh fading channel over the links between devices and the MC. We assume a non-preemptive system in the MC so that the packets with lower priority can be replaced by higher priority packets, as well. The arrival packets have different deadlines due to the diversity of information in the network. The average number of successfully served packets are obtained as the effective traffic intensity of the whole network to measure the performance of the system. The simulation results show that increasing the number of classes with priorities, does increase the traffic intensity up to service rate of the monitoring center.
The effect and mechanism of miRNA-140 in exosomes of hypoxic bone marrow mesenchymal stem cells on articular chondrocytes
Authors: Hu Yuezheng , Liu HaiXiao , Xu Daoliang , Xue Xinhe , Xu Xinxian
Published: June 2022

This study aimed to investigate the effects and mechanisms of miRNA-140 in exosomes of hypoxic bone marrow mesenchymal stem cells on articular chondrocytes. Articular chondrocytes were stimulated with IL-1β (10 μg/ml) to give them an inflammatory state. Exosomes were extracted by differential ultra-high speed centrifugation, and their morphology was identified by transmission electron microscopy. The Cell Counting Kit-8 (CCK-8) assay, cell scratch assay and flow cytometry method were utilized to assess the proliferation, migration and apoptosis of chondrocytes respectively. Expressions of miR-140, HIF-1α mRNA and mRNA associated with chondrocytes were investigated using quantitative reverse transcription PCR (qRT-PCR). Western blot was applied to assess the chondrocyte associated proteins Caspase3, Collagen II, HIF-1α, SOX-9 and BMSC-Exo surface protein markers CD9, CD63, TSG101. To observe effects of inflammatory chondrocytes, immunohistochemistry was adopted to detect the staining of Collagen I and Collagen II. Eventually, exosomes’ shape was almost round, and the scratch healing was significantly increased in BMSC-Exo treated groups compared with the IL-1β group (P < 0.001). Additionally, it was found that exosomes in the hypoxic state (Hypoxia-Exo) resulted in higher cellular activity, less apoptosis and enhanced protein expression in inflammatory chondrocytes compared to the normoxic state (Normoxia-Exo), while weakening adipose differentiation and enhancing chondrogenic differentiation. Furthermore, the healing effect of exosomes on inflammatory chondrocytes under hypoxic conditions was produced by a rise in miR-140 expression within them. In conclusion, under hypoxia, miRNA-140 in bone marrow mesenchymal stem cell exosomes promotes proliferation and migration of chondrocytes and reduces apoptosis of chondrocytes.
Volumetric fluid analysis of fixed monthly anti-VEGF treatment in patients with neovascular age-related macular degeneration
Authors: 홍 인환 , Chang In Boem , Yu Hyeong Gon
Published: June 2022

Background: To evaluate visual outcomes and changes in fluid after administering monthly anti-vascular endothelial growth factor (anti-VEGF) injections to treat neovascular age-related macular degeneration (nAMD) with subretinal fluid (SRF) and pigment epithelial detachment (PED).Methods: This prospective study included eyes with nAMD previously treated with as needed anti-VEGF injections. The patients were treated with six monthly intravitreal injections of ranibizumab. Quantitative volumetric segmentation analyses of the SRF and PED were performed. The main outcome measures included best-corrected visual acuity (BCVA), and SRF and PED volumes.Results: Twenty eyes of 20 patients were included in this study. At the 6-month follow-up, BCVA and PED volume did not change significantly (P = 0.110 and 0.999, respectively) but the mean SRF volume decreased from 0.53 ± 0.82 mm3 at baseline to 0.08 ± 0.23 mm3 (P = 0.002). The absorption rate of the SRF volume was negatively correlated with the duration of previous anti-VEGF treatment (P = 0.029). Seven of the 20 eyes (35%) showed a fluid-free macula and significant improvement in BCVA (P = 0.036) by month 6.Conclusions: Quantifying the SRF can precisely determinine the patient’s responsiveness to anti-VEGF treatment.
Loneliness and suicide risks in the general population in Taiwan
Authors: Hung Wei-Chieh , Wu Chia-Yi , Lee Ming-Been , Chan Chia-Ta , Chen Chun-Ying
Published: June 2022

Purpose Loneliness is a critical issue afflicting the general population. Current evidence from nationwide surveys of loneliness is scarce. This study aimed to investigate the prevalence and risk factors of loneliness in representative surveys across Taiwan.Methods Four annual telephone interview surveys were performed by the Taiwan Suicide Prevention Center in 2015, 2016, 2017, and 2020. Each yearly sample was randomly selected by stratifying the general public over 15 years old in different geographical areas. Participants completed a single-item loneliness screening question and a set of instruments assessing socio-demographic and psychological distress (5-item Brief Symptom Rating Scale), as well as suicide risk (9-item Concise Mental Health Checklist). All the survey data were integrated for analysis.Results In total, 8460 participants (49.4% males) were recruited. Gender, age, job, education, and marital status in the four-year distributions were similar. The average prevalence of loneliness was 12.6%. Loneliness was associated with psychological distress (e.g., insomnia and depression) and suicide risks, being positively correlated with two suicide risk factors, “alcohol/drug abuse” and “no one trustworthy to talk to”, and negatively correlated with self-rated health variables. The odds of loneliness for lifetime suicidal ideation, lifetime suicide attempt, and future suicide intent were 4.9, 5.1, and 9.2, respectively. Conclusion The study highlighted key suicide-related variables of loneliness, particularly the role of future suicide intention, substance use, perceived health, and lack of trusting relationships. Promoting self-perceived health conditions and understanding suicidal ideation over lack of trusting relationships among the general public may reduce feelings of loneliness.
Physical-Model Guided Self-Distillation Network for Single Image Dehazing
Authors: Lan Yunwei , Cui Zhigao , Su Yanzhao , Wang Nian , Li Aihua
Published: June 2022

Image dehazing, as a key prerequisite of high-level computer vision tasks, has gained extensive attention in recent years. Traditional model-based methods acquire dehazed images via atmospheric scattering model, which dehaze favorably but often cause artifacts due to the error of parameter estimation. By contrast, recent model-free methods directly restore dehazed images by building an end-to-end network, which achieve better color fidelity. To combine the merits of these two methods, we propose a physical-model guided self-distillation network for single image dehazing. Specially, we add three early-exit branches on a deep feature extraction network constructed with four attention guided feature extraction blocks to obtain both of model-based dehazed images and model-free dehazed images. Moreover, we propose a two-stage training optimization strategy to combine the features of these intermediate dehazed images, and adopt self-distillation to transfer the features from the deeper layers (perform as teacher) to shallow early-exit branches (perform as student). Experimental results on both synthetic and real-world images demonstrate that the proposed method achieves better dehazing effect when compared with state-of-the-art methods.
Status and progress of Icotinib in treatment of EGFR-mutant non-small cell lung carcinoma
Authors: Zhou Xingwen , Huang Junhao , Zhou Tao
Published: June 2022

Lung cancer has a high incidence and mortality worldwide. Among them, non-small cell lung cancer (NSCLC) accounts for the majority. In terms of treatment, targeted therapy is a more effective option for NSCLC patients with genetic mutations when compared with chemotherapy. Currently, there are a number of targeted drugs targeting different mutations in NSCLC on the market, among which, icotinib (Conmona®) is an oral small molecule epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). It’s approved as first-line treatment for locally advanced or metastatic NSCLC patients with EGFR-mutant, for monotherapy to treat locally advanced or metastatic non-small cell lung cancer (NSCLC) after the failure of at least one prior chemotherapy regimen (primarily platinum-based combination chemotherapy) and approved as postoperative adjuvent therapy for stage Ⅱ-ⅢA NSCLC with EGFR-mutant in China. What’s more, there are many other usages and further clinical trials are underway. Here, we review the status and progress of icotinib in the treatment of EGFR-mutant NSCLC.
The prognostic role of the immunohistochemical expression of S100 in meningiomas
Authors: Behling Felix , Fodi Christina , Skardelly Marco , Paulsen Frank , Tabatabai Ghazaleh , Honegger Jürgen , Tatagiba Marcos , Schittenhelm Jens
Published: June 2022

Background:Despite best clinical management meningioma patients experience tumor recurrence. Efforts have been made to improve the prognostic stratification of meningiomas. Recently a multi-faceted molecular classification suggested that the marker S100 is associated with a favorable outcome, making a further analysis is a larger cohort interesting. Material and Methods:The immunohistochemical staining for S100 was analyzed in 1669 paraffin-embedded meningioma samples. The distribution and association with clinical data and progression-free survival via radiographic tumor recurrence were assessed. Results:Of 1669 cases 218 tumors showed strong S100 expression (13.1%). A significantly higher frequency of S100 positive meningiomas was observed in meningiomas of female patients, tumors with spinal and convexity/falx location, primary tumor surgery, NF2, higher extent of resection, lower WHO CNS grade, adjuvant radiotherapy and recurrence-free tumors during follow-up. Univariate analysis revealed a favorable progression-free survival for meningiomas with S100 expression (p=0.0059) but not in the multivariate analysis. Higher S100 frequency was independently associated with female gender (p=0.0003), NF2 (p<0.0001), tumor location (p<0.0001) and lower WHO CNS grade (p=0.0133).Conclusions:The positive prognostic impact of S100 is mostly attributed to the confounding clinical factors gender, tumor location, NF2 status and WHO CNS grade.
A Polyclonal Antibody Dosing Strategy to Reduce the Viral Load of Multiple Coronavirus Mutants in COVID-19 Patients with Pneumonia
Authors: Kompella Rohini , Patil Madhoosudan
Published: June 2022

Purpose Monoclonal antibodies target a single epitope or region in an antigen for therapeutic purposes. Given the highly mutant nature of SARS-COV-2 or coronavirus, it is likely that a cocktail of antibodies or a polyclonal antibody targeting multiple regions of the virus might be more beneficial in treating COVID-19. The purpose of this project, based on the reported clinical evaluation of XAV-19 polyclonal antibody in pneumonia patients, is to develop a pharmacokinetic-pharmacodynamic (PK-PD) model to explain the relationship between drug concentrations and reduction in the nasopharyngeal viral load. Methods: The concentration of the drug in a time course was related to the effect at each time point to determine the PK-PD relationship. Using Berkeley-Madonna, a PK-PD mathematical model including a central serum compartment, a peripheral effect compartment, and an Emax model for drug effects was developed to explain the observed drug concentrations and effects. Using published EC50 concentrations for XAV-19 and various variants of SARS-CoV-2, the time course of drug effect was predicted for the virus variants including D614G, alpha, beta, gamma, and delta. Results: The results indicated a counterclockwise hysteresis loop for the PK-PD relationship, suggesting lower effects at the same concentration initially, followed by greater effects at the same concentration later. This is consistent with separation of the effect compartment from the serum compartment, where concentrations are measured. The model explained the observed data well. Conclusion: The PK-PD model is useful in predicting dose-response relationships for the new polyclonal antibody. Further, it can be extended to other emerging variants of the coronavirus.
Raw Milk Components and Amino Acid Profiles Considerably Vary among Different Crossbred Dairy Buffaloes
Authors: Islam Md Zakirul , Rahman S. M. Rajiur , Meenongyai Watcharawit , Hasan Md. Sayed , Khandakar Md. Mehedi Hasan , Siddiki Mohammad Shohel Rana , Islam Md. Nurul , Harun-ur-Rashid Md.
Published: June 2022

This study aimed to assess the relationship between milk components and amino acid (AA) profiles among different crossbred buffaloes in Bangladesh. A total of thirty-six (36) lactating buffaloes were selected from Murrah, Nili-Ravi, and Mehsana crossbreds, and 03 groups were made, each with 12 buffaloes. The total experimental period was 10 weeks, including 10 days of diet adjustment. The results revealed that milk protein and total solids contents of Murrah, Mehsana, and Nili-Ravi crossbred buffaloes showed a higher to lower trend (p < 0.05). Considerable variations of milk protein, fat, lactose, and total solids contents were observed among Murrah, Nili-Ravi, and Mehsana crossbred buffalo. The highest amount of amino acid was Glutamic acid (0.9-1.00 g/100 g of milk), and the trace amount of amino acid was Cysteine (0.02–0.05 g/100 g of milk) among all the milk samples. The most prevalent essential amino acids were Leucine, Lysine, and Phenylalanine, whereas the most prevalent non-essential amino acids were Glutamic acid, Proline, Asparagine, and Serine. Lysine, Isoleucine, Leucine, Phenylalanine, Cysteine, and Histidine concentrations differed significantly (p < 0.05) at the same time as the other 11 AA concentrations were found non-significant (p > 0.05). The highest Lysine: Methionine ratio observed in Murrah buffalo is about 3.20%, while in Mehsana and Nili-Ravi buffalo is about 2.80 and 2.50%, respectively. Thus, it is evident from the study that the raw milk components and amino acid composition vary considerably in the different crossbred lactating buffaloes. Finally, the compositional data of raw milk may create the way of sustainable use of milk from crossbred dairy buffaloes and improve food and nutrition security, particularly in developing countries.
Chemo assists for children mobile health application to manage symptoms of chemotherapy in acute leukemia in Indonesia: A user-centered design approach
Authors: Novrianda Dwi , Herini Elisabeth Siti , Haryanti Fitri , Supriyadi Eddy , Lazuardi Lutfan
Published: June 2022

Background: The mobile health (mHealth) application encourages parents and pediatric patients to be involved in caring for their child's health condition by providing the ability to actively identify and manage chemotherapy-induced symptoms in their child. Several monitoring systems available today are diverse in features and system basis. This study aimed to develop and trial the Chemo Assists for Children (CAC) mHealth application for symptom management due to chemotherapy in children with acute lymphoblastic leukemia (ALL).Methods: In this study, the development of the CAC application went through four phases. The initial phase was conducting a literature study for application content. The application design phase involved five experts in validating application content. In the implementation phase, the application was piloted on ten parents with ALL children undergoing chemotherapy at two teaching hospitals in Indonesia. According to the test results, the CAC application was improved at the evaluation stage. The data were obtained descriptively from the validation and application testing using the average and total item scores.Results: Phase 1 obtained 17 reference sources in textbooks and research journal articles to design the mHealth application content. Phase 2 received the value of the content validity of all statements was 0.96, which means that the application material is declared valid. In phase 3, the average total usability test score was 4.28. Finally, an evaluation phase was applied continuously to produce an accurate, accessible, and appropriate application for users.Conclusions: The CAC mHealth application developed can meet the needs of technology users to identify symptoms and manage symptoms due to chemotherapy in children with ALL. The CAC mHealth application can accommodate data not recorded at out-of-hospital care, increase the independence of symptom management, and improve communication between parents of children with ALL and health workers.