bluuebunny/crossref_metadata_2025 huggingface dataset:
THE NEED FOR TRANSFORMING AGRICULTURE PRODUCE MARKETS: EVIDENCE FROM PUNJAB, PAKISTAN
Authors: Bhutta Ehsan
Published: October 2021

The evolution of high-yielding varieties of seeds, increasing use of fertilizers, pesticides, installation of tube-wells and mechanization has increased the agricultural productivity (AP). An efficient agricultural marketing (AM) system increases the growth of agri-business and improves the economic growth. More recently, research has shown that agriculture growth cannot be realized without well- functioning agricultural produce markets (APMs).In Pakistan, however, development of APMs largely remained neglected because of overriding emphasis of public policies on enhancing AP. Consequently, APMs could not be developed adequately and imperfections in the legal structure, management and operations of these markets have limited their performance. A survey was conducted in nine districts of the Punjab province having interviews with staff of market committees (MCs-90), commission-agents (CAs-90), whole-sellers (WS-90) and retailers (RT-90). The results reflect that there is an urgent need for amending legal and institutional mechanism for making APMs efficient. The study will help academia and policy makers to improve efficiency of APMs in the province
Comparison of clinical outcomes achieved with oblique lateral interbody fusion with or without supplementary instrumentation in patients with single-level lumbar degenerative disease
Authors: Lang Zhao , Sun Yuqing , Yuan Qiang , Wu Jingye , Fan Mingxing , Li Jianing , Tian Wei
Published: October 2021

Background

Oblique lateral interbody fusion (OLIF) is applied often to treat degenerative disc disease in the lumbar spine. Stand-alone OLIF prevents morbidities associated with supplemental fixation and is less expensive. However, it remains controversial whether stand-alone OLIF is sufficient to avoid subsidence for single-level diseases. Additionally, bilateral pedicle screw (BPS) and bilateral transfacet screw (BTS) fixation are well-established posterior fixation methods that can offer improved biomechanical stability. But the comparison of clinical outcomes of OLIF with and without supplementary instrumentation is lack.
Methods

We retrospectively examined 20 patients who underwent single-level stand-alone OLIF for symptomatic lumbar degenerative disease at L1–L5 (SA group). Groups of patients treated with OLIF plus BPS (n = 20, BPS group) or BTS (n = 20, BTS group) were matched for age, sex, diagnosis, operative level, body mass index, and bone mineral density. The disk height index (DHI), segmental lordotic (SL) angle, and lumbar lordotic (LL) angle were measured preoperatively and at 3 days and 6 months postoperatively. Clinical outcomes were evaluated.
Results

Significant disc height loss was observed in all groups, but was greater in the SA and BTS groups than in the BPS group at the 6-month follow-up. The SL and LL angles were not affected in any group. The operative time was significantly less in the SA group, and the estimated blood loss was significantly higher in the BPS group. At 6 months post-surgery, improvements in clinical outcomes were evident in all groups, but the VAS (back pain), JOA, and ODI scores were worse in the SA group than in the other groups.
Conclusions

Stand-alone OLIF was associated with greater subsidence and poorer clinical outcomes compared with OLIF plus supplementary instrumentation. The addition of BTS did not decrease the degree of subsidence, but provided clinical outcomes comparable to those achieved with BPS.
Genome-Wide Analysis of BURP Genes and Identification of a BURP-V Gene RcBURP4 in Rosa Chienesis
Authors: Fu Lufeng , Zhang Zhujun , Wang Hai , Zhao Xiaojuan , Su Lin , Geng Lifang , Lu Yizeng , Tong Boqiang , Liu Qinghua , Jiang Xinqiang
Published: October 2021

BURP proteins are unique to plants and may contribute greatly to growth, development, and stress responses of plants. Despite the vital role of BURP proteins, little is known about these proteins in rose (Rosa spp.). In the present study, nine genes belonging to the BURP family in R. chienesis were identified by using multiple bioinformatic approaches against the rose genome database. The nine RcBURPs, with diverse structures, were located on all chromosomes of the rose genome, except for Chr2 and Chr3. Phylogenic analysis revealed that these RcBURPs can be classified into eight subfamilies, including BNM2-like, PG1β-like, USP-like, RD22-like, BURP-V, BURP-VI, BURP-VII, and BURP-VIII. Conserved motif and exon-intron analyses indicated a conserved pattern within the same subfamily. The presumed cis-regulatory elements (CREs) within the promoter region of each RcBURP were analyzed and the results showed that all RcBURPs contained different types of CREs, including abiotic stress-, light response-, phytohormones response-, and plant growth and development-related CREs. Transcriptomic analysis revealed that a BURP-V member, RcBURP4, was induced in rose leaves and roots under mild and severe drought treatments. We then overexpressed RcBURP4 in Arabidopsis and examined its role under abscisic acid (ABA), NaCl, polyethylene glycol (PEG), and drought treatments. Nine stress-responsive genes expression were changed in RcBURP4-overexpressing leaves and roots. Furthermore, RcBURP4-silenced rose plants exhibited decreased tolerance to dehydration. The results obtained from this study provide the first comprehensive overview of RcBURPs and highlight the importance of RcBURP4 in rose plant.
Identification CXCL9 is a Potential Prognostic Biomarker in Ovarian and Gastric Cancer and is Correlated with Immune Infiltrates
Authors: Li Shuwei , Shi Ruijun , Zhou Hangzheng , Wang Dongyang , Zhu Kunlong , Xue Shenglong , Zhang Jianpei , Wu Tinghui , Li Yongchao
Published: October 2021

Background: CXCL9 also known as an interferon gamma-inducible chemokine that belonging to the CXC chemokine family. It plays a role in promoting chemotaxis, inducing leukocyte differentiation and multiplication, and triggering tissue extravasation. Methods: The TIMER (Tumor Immune Estimation Resource) and cancer microarray database Oncomine were used to dig at CXCL9 expression. The clinic prognostic level of CXCL9 was evaluated via Kaplan-Meier plotter. Then, Using TIMER and GEPIA, we investigated whether CXCL9 expression impacted cancer immune infiltrates. Results: CXCL9 expression has been found to be significantly lower in ovarian and gastric cancers relative to normal tissues. In patients with ovarian cancer (OS HR = 0.78, P = 0.0017; PFS HR = 0.85, R = 0.015) and gastric cancer (OS HR = 0.55, P = 1.1e-08; PFS HR = 0.58, R = 7.6e-07), low CXCL9 expression was correlation to PFS (progression-free survival) and OS (poor overall survival). Furthermore, in OV and GC, CXCL9 was shown to have a close interaction with tumor-infiltrating immunity cells (B cells, CD4+ and CD8+ T cells, macrophages, neutrophils, and dendritic cells). CXCL9 expression, on the other hand, was shown to be closely related to several immune markers.Conclusion: In OV and GC, CXCL9 mRNA level is strongly associated with prognosis and levels of penetration tumor-infiltrating immunity cell. The CXCL9 expression may also play a role in controlling TAMs (tumor-associated macrophages), DCs (Dendritic cells), CTLs (cytotoxic lymphocytes), and NK (natural killer) cells in OV and GC. CXCL9 may be seen as an independent marker that assesses the prognosis in OV and GC patients. Besides, CXCL9 expression level also can assess the immune cell subtypes of tumor microenvironment in OV and GC.
IL-6 knockout alleviates inflammatory response and improve acute lung injury via regulating macrophage polarization in sepsis
Authors: Zhang Jinxin , Shen Kuo , Xie Jiangang , Liu Shanshou , Bai Xiaozhi , Wang Jing , Zhao Ming , Li Jin , Li Shaohui , li Junjie , Yin Wen
Published: October 2021

BackgroundSepsis is a fatal disease with a high rate of morbidity and mortality, during which acute lung injury is the earliest and most serious complication. Macrophage plays a crucial role in the initiation and progress of sepsis. This study meant to explore the effect of IL-6 knockout in CLP induced sepsis.MethodsIn this study, cecal ligation and puncture (CLP) was performed on wildtype and interleukin 6 (IL-6) knockout C57 mice. General condition and death rate of sepsis mice were observed. organ samples (lungs, livers, kidneys and hearts) and serum were collected for histology observation and inflammatory cytokine detection. Lung tissue injury detection were conducted via lung injury score, wet/dry ration and protein concentrations measurement of Bronchoalveolar lavage fluid (BALF). In in vivo studies, RAW264.7 macrophages were transfected with IL-6 specific siRNA and treated with LPS. After exposed to IL-6 specific siRNA and LPS, expression of inflammatory cytokines interleukin 1 (IL-1), tumor necrosis factor- (TNF-), IL-6 and interleukin 10 (IL-10) were detected by RT-qPCR, concentration of IL-1 and TNF- in culture supernatant were detected by ELISA and M1 and M2 markers were detected by western blot and flow cytometry.ResultsWe constructed CLP induced sepsis models and found that inhibition of IL-6 could improve general condition and death rate of sepsis mice. Mice in IL-6 knockout group display improved tissue damage, especially in the lung tissue. IL-6 knockout relieved inflammatory cytokines storm in both serum and bronchoalveolar lavage fluid while polarized macrophage to an anti-inflammatory M2 phenotype. In cell model, inhibition of IL-6 could alleviate LPS induced expression of inflammatory cytokines IL-1, TNF-, and IL-6 in macrophages. Western blot and Flow cytometry results indicated that expression of M1 markers (iNOS and CD86) in LPS stimulated macrophages were significantly declined while M2 (Arg-1 and CD206) were enhanced when expression of IL-6 was blocked.Conclusion Inhibition of IL-6 alleviated LPS induced inflammation and exerted protective effect in sepsis via regulating macrophage function and polarization.
Identification a ceRNA (XIST/miR-10a-5p/SERPINE1) Axis as a Prognostic Biomarker in Kidney Renal Clear Cell Carcinoma.
Authors: Liu Rui-ji , Xu Zhi-Peng , Li Shuying , Yu Jun-Jie , Xu Bin , Chen Ming
Published: October 2021

Background: Kidney cancer is one of the most common malignancies, of which the most aggressive subtype was kidney renal clear cell carcinoma (KIRC), accounting for 80% of them. A growing number of studies point to the involvement of competitive endogenous RNAs in tumor development. However, the role of ceRNA network involved in KIRC remains unclear. Thus, the aim of this study was to investigate the BAP1-associated prognostic ceRNA in KIRC. Methods: We downloaded the RNAseq data from TCGA along with the relevant clinical data. We screened the differentially expressed lncRNAs, miRNAs, mRNAs according to the expression of BAP1 and established a ceRNA network. Results: After comprehensive bioinformatics analysis, we identified the XIST-miR-10a-5p-SERPINE1 ceRNA axis. Next, we confirmed the prognostic role of miR-10a-5p/SERPINE1 in KIRC using survival analysis and Cox regression analysis. To investigate the abnormally high expression of SERPINE1, we performed methylation analysis of SERPINE1 and concluded that the methylation level of SERPINE1 in KIRC was significantly lower than that in normal tissues. Furthermore, to study the role of SERPINE1 in the immune microenvironment in KIRC, we performed immune cell infiltration analysis and found that SERPINE1 expression was positively correlated with the level of multiple immune cell infiltration (CD 4+ T cell, CD 8+ T cell, macrophages, dendritic cells, neutrophils). Conclusion: We constructed a ceRNA (XIST/has-miR-10a-5p/SERPINE1) that can be used as prognostic biomarker of KIRC. Furthermore, we found that miR-10a-5p/SERPINE1 were significantly associated with clinical features and were independent prognostic factors of KIRC.
A Baseline Study On The Occurrence And Distribution of Microplastics In The Highly Polluted Metropolitan River Cooum, Chennai, India.
Authors: Ganapathy Velusamy Selva , Radhakrishnan Krishnamoorthy , Prakasheswar Palanichamy
Published: October 2021

The current research aimed to determine the distribution of micro plastics in surface sediments and water from Chennai's Cooum River. The fiber dominates the Cooum River's surface sediments and water, followed by beads and fragments. Both the sediment and the water contain a high concentration of <1mm size micro plastics. The distribution counts of micro plastics in the Cooum River are significantly low compare to those found in the St. River Lawrence and Amazon river brazil. The distribution of micro plastics in riverine environments is strongly influenced by waste water discharge from domestic and industrial sources, as well as waste dumping near riverbanks.
Combination of Artesunate and WNT974 Induces KRAS Protein Degradation by Upregulating E3 Ligase ANACP2 and β-TrCP in the Ubiquitin–Proteasome Pathway
Authors: GONG RUIHONG , Chen Minting , Huang Chunhua Huang , Wong Hoi Leong Xavier , Kwan Hiu Yee , Bian Zhaoxiang Bian
Published: October 2021

BackgroundKRAS mutation is one of the dominant gene mutations in colorectal cancer (CRC). Up to present, targeting KRAS for CRC treatment remains a clinical challenge. WNT974 (LGK974) is a porcupine inhibitor that interferes Wnt signaling pathway. Artesunate (ART) is a water-soluble semi-synthetic derivative of artemisinin.MethodsThe synergistic effect of ART and WNT974 combination in reducing CRC cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RT-PCR was utilized for the mRNA levels of KRAS, CUL7, ANAPC2, UBE2M, RNF123, SYVN1, or β-TrCP. Western blot assay was utilized for the protein levels of KRAS, ANAPC2, β-TrCP, or GSK-3β. Xenograft mouse model assay was performed for the anti-CRC effect of combination of ART and WNT974 in vivo. IHC assay was utilized for the levels of KRAS, β-TrCP, or GSK-3β in tumor tissues. Results Our study shows that the combination of WNT974 and ART exhibits synergistic effect in reducing CRC growth. The combination treatment significantly reduces KRAS protein level and activity in CRC cells. Interestingly, the combination treatment increases E3 ligases ANAPC2 expression. Our data show that overexpression of ANAPC2 significantly reduces KRAS protein levels, which is reversed by MG132. Knockdown of ANAPC2 in CRC abolishes the combination treatment-reduce KRAS expression. Besides, the treatment also increases the expressions of GSK-3β and E3 ligase β-TrCP that is known to degrade GSK-3β-phosphorylated KRAS protein. Knockdown of β-TrCP- and inhibition of GSK-3β abolish the combination treatment-induce KRAS ubiquitination and reduction in expression.ConclusionsOur data clearly show that the combination treatment significantly enhances KRAS protein degradation via the ubiquitination ubiquitin–proteasome pathway, which is also demonstrated in xenograft mouse model. The study provides strong scientific evidence for the development of the combination of WNT974 and ART as KRAS-targeting therapeutics for CRC treatment.
Natural Images Allow Universal Adversarial Attacks on Medical Image Classification Using Deep Neural Networks With Transfer Learning
Authors: Minagi Akinori , Hirano Hokuto , Takemoto Kazuhiro
Published: October 2021

Background. Transfer learning from natural images is well used in deep neural networks (DNNs) for medical image classification to achieve computer-aided clinical diagnosis. Although the adversarial vulnerability of DNNs hinders practical applications owing to the high stakes of diagnosis, adversarial attacks are expected to be limited because training data — which are often required for adversarial attacks — are generally unavailable in terms of security and privacy preservation. Nevertheless, we hypothesized that adversarial attacks are also possible using natural images because pre-trained models do not change significantly after fine-tuning.Methods. We considered three representative DNN-based medical image classification tasks (i.e., skin cancer, referable diabetic retinopathy, and pneumonia classifications) to investigate whether medical DNN models with transfer learning are vulnerable to universal adversarial perturbations (UAPs), generated using natural images.Results. UAPs from natural images are useful for both non-targeted and targeted attacks. The performance of UAPs from natural images was significantly higher than that of random controls, although slightly lower than that of UAPs from training images. Vulnerability to UAPs from natural images was observed between different natural image datasets and between different model architectures.Conclusion. The use of transfer learning causes a security hole, which decreases the reliability and safety of computer-based disease diagnosis. Model training from random initialization (without transfer learning) reduced the performance of UAPs from natural images; however, it did not completely avoid vulnerability to UAPs. The vulnerability of UAPs from natural images will become a remarkable security threat.
Laparoscopic Management of Benign Colorectal Diseases
Authors: Shaheen Mahmoud , Zeineldin Ashraf , Ghazal Abd Elhamid , ElFol Hossam , Arafa Ahmed
Published: October 2021

Background: Laparoscopic colectomy is safe and effective, and in some cases, superior to open surgery, for a range of benign illnesses. The short-term advantages include less gastrointestinal discomfort, decreased wound infection and surgical morbidity, quicker bowel function restoration, and a shorter duration of hospital stay.Aim of the work & Methodology: evaluate our practice in laparoscopic colectomy by studied 20 patients with benign colorectal disorders admitted to our university hospital between Dec. 2015 and Dec. 2020. Inclusion criteria: 1. Age ranging from 15 to 70 years. 2. Patients with benign colorectal diseases, e.g., diverticular diseases, inflammatory bowel diseases, colonic polyps, rectal prolapse, etc. Exclusion criteria; malignant colorectal tumors and relative contraindication for laparoscopy. We were using classical laparoscopic techniques. Patients were discharged from the hospital when they could tolerate a regular diet. They were followed up at least six months, starting on the 30th postoperative day on a regular visit every two weeks—the data recorded including the intraoperative events and the difficulties and postoperative follow-up.Results: Technical difficulties are more remarkable for benign conditions than for cancer, especially for patients with inflammatory bowels, such as diverticular disease or inflammatory bowel disease, which frequently involve adjacent structures, peri-colic fibrosis, and lost planes. Surgeons should choose their patients before beginning laparoscopic colorectal surgeries.Conclusions: Laparoscopic surgery provides numerous advantages over open surgery, including minor discomfort, a shorter hospital stay, reduced morbidity, and a faster postoperative recovery. Our study cannot be utilized in a comparison study since it only evaluates our practice, and the findings may not be generalizable.
Identification and Validation of a QTL for Spikelet Number on Chromosome Arm 6BL of Common Wheat (Triticum Aestivum L.)
Authors: Katz Andrew , Byrne Patrick , Reid Scott , Bratschun Sarah , Haley Scott , Pearce Stephen
Published: October 2021

To provide food security for a growing world population, it will be necessary to increase yields of staple crops such as wheat (Triticum aestivum L.). Yield is a complex, polygenic trait influenced by grain weight and number, which are negatively correlated with one another. Spikelet number is an important determinant of grain number, but allelic variants impacting its expression are often associated with heading date, constraining their use in wheat germplasm that must be adapted for specific environments. Identification and characterization of genetic variants affecting spikelet number will increase selection efficiency through their deployment in breeding programs.In this study, a quantitative trait locus (QTL) on chromosome arm 6BL for spikelet number was identified and validated using an association mapping panel, a recombinant inbred line population, and seven derived heterogeneous inbred families. The superior allele, QSn.csu-6Bb, was associated with an increase of 0.248 to 0.808 spikelets per spike across multiple environments that varied for mean spikelet number. Despite epistatic interactions between QSn.csu-6B and three other loci (WAPO-A1, VRN-D3 and PPD-B1), genotypes with a greater number of superior alleles at these loci consistently exhibit higher spikelet number. The frequency of superior alleles at these loci varies among winter wheat varieties adapted to different latitudes of the United States Great Plains, revealing opportunities for breeders to select for increased spikelet number using simple molecular markers. This work lays the foundation for the positional cloning of the genetic variant underlying the QSn.csu-6B QTL to strengthen our understanding of spikelet number determination in wheat.
Transmembrane p24 Trafficking Protein 2 Regulates Inflammation Through the TLR4/NF-κB Signaling Pathway in Lung Adenocarcinoma
Authors: Feng Longhua , Cheng Pengjiang , Feng Zhengyun , Zhang Xiaoyu
Published: October 2021

Background: To investigate the role of transmembrane p24 trafficking protein 2 (TMED2) in lung adenocarcinoma (LUAD) and determine whether TMED2 knockdown could inhibit LUAD in vitro and in vivo.Methods: TIMER2.0, Kaplan-Meier plotter, gene set enrichment analysis (GSEA), Target Gene, and pan-cancer systems were used to predict the potential function of TMED2. Western blotting and immunohistochemistry were performed to analyze TMED2 expression in different tissues or cell lines. The proliferation, development, and apoptosis of LUAD were observed using a lentivirus-mediated TMED2 knockdown. Bioinformatics and western blot analysis of TMED2 against inflammation via the TLR4/NF-κB signaling pathway were conducted. Results: TMED2 expression in LUAD tumor tissues was higher than that in normal tissues and positively correlated with poor survival in lung cancer and negatively correlated with apoptosis in LUAD. The expression of TMED2 was higher in tumors or HCC827 cells. TMED2 knockdown inhibited LUAD development in vitro and in vivo and increased the levels of inflammatory factors via the TLR4/NF-κB signaling pathway. TMED2 was correlated with TME, immune score, TME-associated immune cells, their target markers, and some mechanisms and pathways, as determined using the TIMER2.0, GO, and KEGG assays.Conclusions: TMED2 may regulate inflammation in LUAD through the TLR4/NF-κB signaling pathway, and enhance the proliferation, development, and prognosis of LUAD by regulating inflammation, which provide a new strategy for treating LUAD by regulating inflammation.
Short-term Results of a New Anatomic Stemless Shoulder Arthroplasty- A Prospective Multicentre Study
Authors: Smith Tomas , Ellwein Alexander , Karkosch Roman , Tsamassiotis Spiros , Horstmann Hauke , Browsher Nina , Pastor Marc-Frederic
Published: October 2021

Background: Anatomic total shoulder arthroplasty (TSA) has been continuously developed and current designs include stemless or canal-sparing humeral components. In the literature stemless and canal sparing TSA showed good clinical and radiographic results, which were comparable to stemmed TSA. The aim of this study was to determine the short-term clinical and radiological outcomes of a new stemless TSA design. Methods: A prospective multicentre study including 154 total shoulder arthroplasty patients with a follow up of 12 months was performed. At the time of follow up 129 patients were available for review. The adjusted Constant Murley score [33], Oxford shoulder score, EQ-5D-5L score and radiographs were examined preoperatively, 3 and 12 months after the implantation of the new stemless TSA implant GLOBAL ICON™ (DePuy Synthes, Warsaw, IN, USA). Complications were documented.Results: Implant Kaplan-Meier survivorship was 98.7% at 12 months. From baseline to 12 months follow-up, all scores showed a progressive significant mean improvement. The mean adjusted Constant score increased from 42.3 to 96.1 points (p<0.001). The Oxford shoulder score showed an increase of 21.6 points (p<0.001). The postoperative radiographs showed no continuous radiolucent lines, subsidence, aseptic loosening or progressive radiolucency, but one osteolytic lesion was observed. Only 2 prostheses were revised. Conclusion: The new GLOBAL ICON stemless TSA showed good clinical and radiographic results at short-term follow up which were comparable to early results of other stemless TSA. Further studies with longer follow up are needed in the future.
Service Migration Algorithm Based On Markov Decision Process With Multiple QoS Attributes
Authors: Ma Anhua , Pan Su , Tao Shuai , Zhou Weiwei
Published: October 2021

With the rapid development of mobile internet cloud computing, the traditional network structure becomes non-suitable for advanced network traffic requirements. A service migration decision algorithm is proposed in the Software Defined Network(SDN) to satisfy differential Quality of Service(QoS) requirements. We divide services into real-time ones and non-real-time ones due to their different requirements on time delay and transmission rates, and construct the revenue function on two QoS attributes i.e. time delay and available transmission rates. We use the Markov decision process to maximize the overall benefits of users and network system to achieve the best user experience. The simulation results show that our proposed algorithm achieves better performance in terms of overall benefits than the exiting algorithms only considering single service and single QoS attribute.
Cascade process mediated by left hippocampus and left superior frontal gyrus affects relationship between aging and cognitive dysfunction
Authors: Kokudai Yumika , Honma Motoyasu , Masaoka Yuri , Yoshida Masaki , Sugiyama Haruko , Yoshikawa Akira , Koiwa Nobuyoshi , Kubota Satomi , Iizuka Natsuko , Wada Sayaka , Kamijo Shotaro , Uchida Yuki , Yano Satoshi , Ida Masahiro , Ono Kenjiro , Izumizaki Masahiko
Published: October 2021

Background: Cognitive function declines with age and has been shown to be associated with atrophy in some brain regions, including the prefrontal cortex. However, the details of the relationship between aging and cognitive dysfunction are not well understood.Methods: Across a wide range of ages (24- to 85-years-old), this research measured the gray matter volume of structural magnetic resonance imaging data in 39 participants, while some brain regions were set as mediator variables to assess the cascade process between aging and cognitive dysfunction in a path analysis.Results: Path analysis showed that age affected the left hippocampus, thereby directly affecting the left superior frontal gyrus. Furthermore, the gyrus directly affected higher order flexibility and maintenance abilities calculated as assessed in the Wisconsin card sorting test, and the two abilities affected an assessment of general cognitive function. Conclusion: Our finding suggests that a cascade process mediated by the left hippocampus and left superior frontal gyrus is involved in the relationship between aging and cognitive dysfunction.
Prognostic Impact of Pneumonitis After Durvalumab Therapy in Patients With Locally Advanced Non-small Cell Lung Cancer
Authors: Nishimura Ari , Ono Akira , Wakuda Kazushige , Kawabata Takanori , Yabe Michitoshi , Miyawaki Taichi , Miyawaki Eriko , Kodama Hiroaki , Nishioka Naoya , Mamesaya Nobuaki , Kobayashi Haruki , Omori Shota , Kenmotsu Hirotsugu , Naito Tateaki , Murakami Haruyuki , Harada Hideyuki , Takahashi Toshiaki
Published: October 2021

Background: Prognostic data on Japanese patients receiving durvalumab after chemoradiotherapy (CRT) for locally advanced non-small cell lung cancer (LA-NSCLC) are insufficient. Whether pneumonitis has prognostic implications in patients with LA-NSCLC who have received durvalumab also remains unclear.Methods: We retrospectively assessed the data of 82 patients who had received durvalumab after CRT at our institution between May 2018 and August 2020. A multi-state model was used to establish the associations between co-variables and progression-free survival (PFS).Results: The median observation period for all the censored cases was 14.5 months (5.7-28.9 months), the median PFS was 22.7 months, and the 12-month PFS rate was 62.3% (95% CI: 50.2%-72.3%). The median percentage of the lung volume receiving a radiation dose in excess of 20 Gray (V20) was 22% (4%-35%). Thirteen patients (16%) had Grade 1 pneumonitis before receiving durvalumab, and 62 patients developed pneumonitis after durvalumab (Grades 1, 2, and 3 in 25 [30%], 32 [39%], and 4 [5%], respectively). Twenty-four patients (29%) completed the 1-year durvalumab treatment period, 16 patients (20%) were continuing to receive treatment, and 42 (51%) had discontinued treatment. In a multi-state analysis, patients with pneumonitis before durvalumab therapy had a poorer PFS than those without pneumonitis (HR: 4.29, p = 0.002). The development of Grade 2 or higher pneumonitis after durvalumab was not a significant prognostic factor for PFS (HR: 0.71, p = 0.852).Conclusion: Grade 2 or higher pneumonitis after durvalumab was not a prognostic factor of PFS in LA-NSCLC patients received durvalumab.
Pigmentation Effects of Kaliziri Standard Extracts on Melanocytes, C57BL/6 mice of Hydroquinone- Induced and Guinea Pigs of Hydrogen Peroxide-Induced Hyperpigmentation Model
Authors: Zang Deng , Maimaiti Zulipiya , Mamat Nuramina , Ma Xiaoling , Li Haorong , Lu Xueying , Turak Ablajan , Luo Yuqin , Aisa Haji Akber
Published: October 2021

Background: Vitiligo is a depigmentation disorder characterized by losing functional melanocytes, leading to skin and/or hair depigmentation. Kaliziri (Vernonia anthelmintica (L.) Willd) seeds have been traditionally used to treat pigmentation disorders in Central Asia. The extracts of these seeds increased melanin content and tyrosinase activity and upregulated melanogenesis-related proteins in B16 melanoma cells. We isolated the main active compound Kaliziri standard Extracts (encoded as CAM-Y7) from the Kaliziri seeds in a previous study. Our goal was to reveal whether CAM-Y7 promotes melanogenesis in melanocytes and restored pigmentation in animal models of vitiligo. Methods: Herein, we analyzed the melanogenic effects of CAM-Y7 on melanocytes and the skin pigmentation of hydroquinone (H.Q.)-induced mouse model and hydrogen peroxide (H2O2)-induced guinea pig model of vitiligo. Results: CAM-Y7 promotes Melanogenesis up-Regulation MITF-induced Tyrosinase Expression via p38MAPK signal pathway in melanocytes. Oral administration of CAM-Y7 progressively darkened the dorsal skin and hair of the C57BL/6 mice and guinea pigs. Lillie staining and hematoxylin-eosin staining further showed that CAM-Y7 induced melanogenesis in the epidermis and hair follicles of the animals. Conclusion: Taken together, these results suggest that CAM-Y7 regulation of melanogenesis may be mediated by the activation of p38 MAPK and restored pigmentation in an HQ-Induced C57BL/6 mouse and H2O2-induced guinea pig models of vitiligo. CAM-Y7 might be valuable and promising therapeutic as an agent for vitiligo. Subsequent clinical experiments using are needed to verify our results.
Risk Factors and Management Strategies of Cerebrospinal Fluid Leakage Following Lumbar Posterior Surgery
Authors: tang jin , lu qilin , li ying , wu congjun , li xugui , gan xuewen , xie wei
Published: October 2021

Objective: To analyze the risk factors of cerebrospinal fluid leakage(CSFL) following lumbar posterior surgery and summarize the related management strategies. Methods: A retrospective analysis was performed on 3179 patients with CSFL strategies lumbar posterior surgery in our hospital from January 2019 to December 2020. There were 807 cases of lumbar disc hemiation(LDH), 1143 cases of lumbar spinal stenosi (LSS), 1122 cases of lumbar spondylolisthesis(LS), 93 cases of lumbar degenerative scoliosis(LDS),14 cases of lumbar spinal benign tumor(LST). Data of gender, age, body mass index(BMI), duration of disease, diabete,smoking history, preoperative epidural hormone injection, number of surgical levels, surgical methods (total laminar decompression, fenestration decompression), revision surgery, extubation time, suture removal time, and complications were recorded.Results: The incidence of 115 cases with cerebrospinal fluid leakage,was 3.62% (115/3179).One-way ANOVA showed that gender, body mass index(BMI), smoking history, combined with type 2 diabetes and surgical method had no significant effect on CSFL(P >0.05). Age, type of disease, duration of disease, preoperative epidural hormone injection, number of surgical levels and revision surgery had effects on CSFL(P<0.05). Multivariate Logistic regression analysis showed that type of disease, preoperative epidural hormone injection, number of surgical levels and revision surgery were significantly affected CSFL(P<0.05), and duration of disease and age of the patients were not significantly affected CSFL (P >0.05).The extubation time of CSFL patients ranged from 7 to 11 days, with an average of 7.11±0.48 days, the extubation time of patients without CSFL was 1-3 days, with an average of 2.02±0.13 days, and there was a statistical difference between the two groups(P < 0.05).The removal time of CSFL patients was 12-14 days, with an average of 13.11±2.67 days, and the removal time of patients without CSFL was 10-14 days, with an average of 12.87±2.19 days, there was no statistically significant difference between the two groups (P>0.05). Conclusion: Type of disease, preoperative epidural hormone injection, number of surgical levels and revision surgery were the risk factors for CSFL. Effective prevention were the key to CSFL in lumbar surgery.Once appear, CSFL can also be effectively dealt with without obvious adverse reactions after intraoperative effectively repair dural, head down, adequate drainage after operation, the high position, rehydration treatment, and other treatments.
Comparative Studies of Carbon Materials Synthesized From Waste as Catalysts for Ozonation of Real Textile Wastewater
Authors: Juwar Vijay A. , RATHOD AJIT , Kodape Shyam M.
Published: October 2021

In the present work, evaluation of two catalysts, Activated carbon (AC) synthesized from agricultural waste and Multiwalled carbon nanotubes (MWCNT) synthesized from plastic waste, were done for the ozonation of real textile wastewater using para- chloro benzoic acid (p-CBA) as a probe compound. The effect of pH and catalyst dose were studied in terms of •OH exposure, Rct, rate of p-CBA degradation and ozone degradation. The rate constant for the reaction of organic matter with hydroxyl radicals was determined using competition kinetics. The threshold ozone dose for real textile wastewater was found to be 0.51 gm/gm of TOC. With an increase in specific ozone dose, the rate of p-CBA degradation was found to be increasing and has shown a positive effect on •OH exposure and Rct. The increasing pH had shown a positive effect on the rate of degradation and decomposition of p-CBA and ozone respectively in the case of AC catalyzed ozonation. A similar trend was observed in the case of MWCNTs catalyzed ozonation. A positive effect of pH was observed on •OH exposure and Rct, in AC as well as MWCNTs catalyzed ozonation. The effect of catalyst loading has shown significant enhancement in p-CBA degradation, ozone decomposition, •OH exposure and Rct in both AC as well as MWCNTs catalyzed ozonation. However, MWCNTs have proved better than AC as a catalyst for ozonation in studied experimental parameters.
Full-length Transcriptome Reconstruction Reveals Genetic Differences in Hybrids of Oryza Sativa and Oryza Punctata With Different Ploidy and Genome Compositions
Authors: He Wenting , Zhang Xianhua , Lv Pincang , Wang Wei , Wang Jie , He Yuchi , Song Zhaojian , Cai Detian
Published: October 2021

Background: Allopolyploid breeding is an efficient technique for improving the low seeding rate of autotetraploids in plant breeding and one of the most promising breeding methods. However, there have been few comprehensive studies of the posttranscriptional mechanism in allopolyploids.Results: By crossing cultivated rice (Oryza sativa, genome AA) with wild rice (Oryza punctata, genome BB), we created hybrid rice lines with different ploidy and genome compositions [diploid F01 (AB), allotetraploid F02 (AABB) and F03 (AAAB)]. The genetic differences of the hybrids and the mechanism of allopolyploid breeding dominance were revealed through morphological and cytological observations and single molecule real-time sequencing techniques. The tissues and organs of allotetraploid rice F02 exhibited "gigantism" and the highest levels of fertility. The numbers of non-redundant transcripts, gene loci and new isoforms in the polyploid rice lines were higher and the isoform lengths greater than those of the diploid line. Moreover, alternative splicing (AS) events occurred twice as often in the polyploid rice lines than the diploid line. During these events, intron retention dominated. Furthermore, a large number of new genes and isoforms specific to the lines of different ploidy were discovered. Conclusions: The results indicated that alternative polyadenylation (APA) and AS events contributed to the complexity and superiority of polyploids in the activity of translation regulators, nucleic acid binding transcription factor activities and the regulation of molecular function. Therefore, these APA and AS events in allopolyploid rice were found to play a role in regulation. Our study provides new germplasm for polyploid rice breeding and reveals complex regulatory mechanisms that may be related to heterosis and fertility.
Association between glycemic control and risk of venous thromboembolism in diabetic patients: A nested case-control study
Authors: Charlier Sarah H R , Meier Christian , Jick Susan S , Meier Christoph R , Becker Claudia
Published: October 2021

Background:Previous studies suggested an elevated risk of venous thromboembolism (VTE) among patients with type 2 diabetes mellitus (T2DM), with a possible sex difference. The impact of glycemic control on the risk of VTE is unclear. Our objective was to analyze the association between glycemic control and the risk of unprovoked (idiopathic) VTE in men and women with T2DM.Methods:We conducted a nested case-control analysis (1:4 matching) within a cohort of patients with incident T2DM between 1995–2019 using data from the CPRD GOLD. We excluded patients with known risk factors for VTE prior to onset of DM. Cases were T2DM patients with an unprovoked treated VTE. The exposure of interest was glycemic control measured as HbA1c levels. We conducted conditional logistic regression analyses adjusted for several confounders.Results:We identified 3’896 VTE cases and 15’584 controls (56% females). We found no association between the HbA1c level and the risk of VTE in our main analysis. However, when the most recent HbA1c value was within 90 days before the index date, women with HbA1c levels > 7.0% had an 18–35% increased relative risk of VTE when compared to women with HbA1c > 6.5-7.0%.Conclusions:Our study raises the possibility that female T2DM patients with HbA1c levels > 7% may have a slightly higher risk for unprovoked VTE compared to women with HbA1c level > 6.5-7.0%. This increase may not be causal and may reflect differences in life style or other characteristics. We observed no effect of glycemic control on the risk of VTE in men.
Breaking the “hard-to-abate” bottleneck in China’s path to carbon neutrality
Authors: Yang Xi , Nielsen Chris , Song Shaojie , McElroy Michael , Wang Xiaoyang
Published: October 2021

Countries such as China are facing a bottleneck in paths to carbon neutrality: abating emissions in heavy industries and heavy-duty transport. There are few in-depth studies of the prospective role for clean (green/blue) hydrogen in these “hard-to-abate” (HTA) sectors. Are current mitigation technologies in HTA sectors effective? What are the roles for clean hydrogen towards carbon neutrality? We carry out an integrated modeling analysis to answer these questions. Results show that, first, clean hydrogen as both energy carrier and feedstock can significantly reduce heavy industry emissions. Second, clean hydrogen can fuel up to 50% of China’s heavy-duty truck and bus fleets by 2060 together with significant shares of shipping. As a side benefit, a realistic hydrogen scenario, reaching 65.7 Mt of production in 2060, could avoid $1.72 trillion new investment cost compared to a no-hydrogen scenario. This study provides strong evidence for countries facing challenges similar to China in addressing requirements to reduce emissions from their recalcitrant HTA sectors towards carbon neutrality.
SIRT3 Protects Against Cognitive Dysfunction Induced by Sepsis-Associated Encephalopathy via JNK/p66Shc-Regulated Mitochondrial Apoptosis in Mice
Authors: Lyu Zhuochen , Luo Shiyuan , Li Yinjiao , Yao Liangfang , Chen Feng , Tu Qing , Yuan Yuan , Li Jinbao , Luo Yan
Published: October 2021

Background
Sepsis-associated encephalopathy (SAE) is one of the severe central nervous system complications. Oxidative stress and synaptic dysfunction were involved in cognitive impairment induced by SAE. The mitochondrial nicotinamide adenine dinucleotide (NAD+) dependent deacetylase, sirtuin3 (SIRT3), plays a critical role in regulating mitochondrial function. The aim of this study was to evaluate the effect of SIRT3 in cognitive dysfunction induced by SAE.
Methods
Mice were treated with lipopolysaccharide (LPS, 10 mg/kg, i.p.). Contextual and cue memory were evaluated by fear conditioning test in wild-type (WT) and SIRT3-deficient (SIRT3-/-) mice. Synapse-associated proteins and mitochondrial apoptosis-associated protein were examined by western blotting. In vitro studies, acetylation levels of cyclophilin D (CypD) were detected with different SIRT3 deacetylase activity in HT22 cells after LPS-induced microglia supernatant (Mi-sup) exposure. Oxidative stress was detected by reactive oxygen species (ROS) staining, and mitochondrial membrane potential (MMP) was detected by JC-1 staining, and mitochondrial membrane permeability transition pore (MPTP) opening was detected by Calcein and Co2+ staining. Furthermore, the phosphorylation levels of mitochondrial p66Shc and JNK were evaluated by western blotting.
Results
SIRT3 expression was diminished in hippocampus of mice after LPS treatment. SIRT3-deficiency contributed to more severe contextual memory loss and synaptic dysfunction, decreased ratio of Bcl-2/Bax and increased Cyt C release to cytoplasm in hippocampus compared with wild-type controls. In HT22 cells, lysine acetylation levels of CypD were significantly increased after Mi-sup exposure and further enhanced with 3-TYP (SIRT3 deacetylation inhibitor) pretreatment, in association with the accumulation of ROS, declined MMP and increased MPTP opening, as well as the increased mitochondrial Cyt C release and phosphorylation levels of mitochondrial JNK and p66Shc-Ser36. SIRT3 overexpression restored CypD lysine acetylation levels and MPTP opening in HT22 cells after Mi-sup exposure and reduced mitochondrial JNK and p66Shc activation.
Conclusion
Taken together, our results showed that SIRT3-mediated CypD deacetylation was involved in LPS-induced hippocampal synaptic dysfunction, via ROS accumulation, declined MMP, increased MPTP opening, mitochondrial Cyt C release and mitochondrial apoptosis of hippocampal neuron via JNK/p66Shc pathway. Our results revealed that SIRT3 may be a promising therapeutic and diagnostic target for cognitive dysfunction induced by SAE.
Palmitate Enhances The Efficacy of Cisplatin And Doxorubicin Against Human Endometrial Carcinoma Cells
Authors: Wu Zihsyuan , Huang Shinming , Wang Yuchi
Published: October 2021

Background: Endometrial cancer is the most common gynecological cancer worldwide. Overexpression of fatty acid synthase is a common molecular feature of a subgroup of sex steroid-related cancers associated with poor prognoses, including endometrial cancers. The saturated fatty acid palmitate reportedly induces lipotoxicity and cell death by inducing oxidative stress in many cell types. Here, we explored the effects of palmitate combined with doxorubicin or cisplatin in the HEC-1-A and RL95-2 human endometrial cancer cell lines. Methods: Endometrial cancer cells were cultured with in vitro and treated with palmitate, doxorubicin, and cisplatin. Cell metabolic activity and combination index was measured using MTT assay. Protein expression was assessed with western blotting. Flow cytometry was used to examine the cell cycle profiles, cell proliferation, apoptosis, ROS, mitochondria membrane potential, and mitochondrial mass. Immunocytochemistry was used to investigate the mitochondrial morphology.Results: Physiological concentrations of exogenous palmitate significantly increased cell cycle arrest, DNA damage, autophagy and apoptosis in both RL95-2 and HEC-1-A cells. It also increased the chemosensitivity of both cell types. Notably, we did not observe that palmitate lipotoxicity reflected increased levels of reactive oxygen species, suggesting palmitate acts via a different mechanism in endometrial cancer.Conclusion: This study provides a potential therapeutic strategy in which palmitate is used as an adjuvant in the treatment of endometrial cancer.
Mentalization and Dissociation after Adverse Childhood Experiences
Authors: Wagner-Skacel Jolana , Riedl David , Kampling Hanna , Lampe Astrid
Published: October 2021

Background: Impairment of mentalization may impact coping strategies, regulation of affect and stress. So far, little is known about the influence of impaired mentalization on dissociation in patients with adverse childhood experiences (ACEs). The aim of this study is to assess the relationship between ACEs, mentalizing and dissociation in adult individuals.
Methods: Sixty-seven patients with ACEs completed the Mentalization Questionnaire (MZQ), the Essener Trauma Inventory (ETI) and the Brief Symptom Inventory-18 (BSI-18). The SPSS PROCESS macro tool was applied to test if mentalization mediated the relationship of ACEs and dissociation.
Results: ACEs were significantly associated with higher dissociation (β=.42, p<.001) and lower mentalization (β=-.49, p<.001). When mentalization was added to the model as a predictor, the association of ACEs with dissociation was no longer significant (β=.11, p=.31) and a statistically significant indirect effect was found (β=.32, 95% CI: .16-.47). The overall explained variance of dissociation notably improved after inclusion of mentalization (17.5% to 49.1%). Thus, the results indicated that the association of ACEs on dissociation was fully mediated by mentalization.
Conclusion: Our results suggest that ACEs are associated with lower mentalization and higher dissociation. Lower mentalization was also associated with worse depression, anxiety, somatization and PTSD symptoms. These findings underline the increasing importance of early treatment of individuals affected by ACDs with a focus to foster the development of mentalization.
Microbial Cysteine Degradation Drives Cryptic Sulfide Redox Chemistry in the Gut
Authors: Wolfson Sarah , Hitchings Reese , Peregrina Karina , Cohen Ziv , Khan Saad , Yilmaz Tugba , Malena Marcel , Goluch Edgar , Augenlicht Leonard , Kelly Libusha
Published: October 2021

Although microbial biochemistry shapes a dynamic environment in the gut, how bacterial metabolites such as hydrogen sulfide (H2S) mechanistically alter the gut chemical landscape is poorly understood. Here we show for the first time that H2S generated during cysteine metabolism drives the reduction of azo (R-N=N-R’) xenobiotics in bacterial cultures, human fecal microbial communities, and in vivo mouse models. Thus, chemical-chemical interactions, derived from microbial community metabolism, are a key missing feature shaping xenobiotic metabolism in the gut. Changing dietary levels of the H2S xenobiotic redox partner Red 40 transiently decreases mouse fecal sulfide, confirming that a xenobiotic can attenuate sulfide concentration in vivo. Cryptic H2S redox thus modulates sulfur homeostasis in the gut and the fate of xenobiotics to which humans are regularly exposed.