bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ubiquitin-specific protease 29 attenuates hepatic ischemia-reperfusion injury by mediating TGF-β-activated kinase 1 deubiquitination
Authors: Chen Zhongbao , Hu Fengjiao , Zhang Yalong , Zhang Long , Wang Tianyu , Kong Chenyang , Hu Haochong , Guo Jiayu , Chen Qi , Yu Bo , Liu Yiting , Zou Jilin , Zhou Jiangqiao , Qiu Tao 
Published: May 2023

Background and aimsIn the course of clinical practice, hepatic ischemia/reperfusion (I/R) injury is a prevalent pathophysiological event and is caused by a combination of complex factors that involve multiple signaling pathways such as MAPK and NF-κB. USP29 is a deubiquitinating enzyme important during the development of tumors, neurological diseases, and viral immunity. However, it is unknown how USP29 contributes to hepatic I/R injury.Methods and resultsWe systematically investigated the role of the USP29/TAK1-JNK/p38 signaling pathway in hepatic I/R injury. We first found reduced USP29 expression in both mouse hepatic I/R injury and the primary hepatocyte hypoxia-reoxygenation (H/R) models. We established USP29 full knockout mice (USP29-KO) and hepatocyte-specific USP29 transgenic mice (USP29-HTG), and we found that USP29 knockout significantly exacerbates the inflammatory infiltration and injury processes during hepatic I/R injury, whereas USP29 overexpression alleviates liver injury by decreasing the inflammatory response and inhibiting apoptosis. Mechanistically, RNA sequencing results showed the effects of USP29 on the MAPK pathway, and further studies revealed that USP29 interacts with TAK1 and inhibits its k63-linked polyubiquitination, thereby preventing the activation of TAK1 and its downstream signaling pathways. Consistently, 5z-7-Oxozeaneol, an inhibitor of TAK1, blocked the detrimental effects of USP29 knockout on H/R-induced hepatocyte injury, further confirming that USP29 plays a regulatory role in hepatic I/R injury by targeting TAK1.ConclusionOur findings imply that USP29 is a therapeutic target with promise for the management of hepatic I/R injury via TAK1-JNK/p38 pathway-dependent processes.
Comparison of oral sodium phosphate tablets and polyethylene glycol lavage solution for colonoscopy preparation: a systematic review and meta-analysis of randomized clinical trials
Authors: Yao-dong Li , Yi-ping Wang , Gang Mai , Yang-yun Han , Ling-ling Zhu , Hong Deng , Jia-zheng Deng , Rong-chao Xiang , You-wei Li , Ming Zhao , Shun-bin Ding , Jing Ling , Yang Shen , Jia-qi Dong , Lei Deng , Xiong-feng Song , You-jian Zhang , Zuo-qiong Zhou 
Published: May 2023

ObjectiveTo systematically compare the bowel cleaning ability, patient tolerance and safety of oral sodium phosphate tablets (NaPTab) and oral polyethylene glycol electrolyte lavage solution (PEGL) to inform clinical decision making.MethodsPubMed, Embase, CBM, WanFang Data, CNKI, and VIP databases were searched for studies that used randomized controlled trials (RCTs) to compare the roles of NaPTab and PEGL in bowel preparation before colonoscopy. Two reviewers independently screened the studies, extracted data, and assessed the risk of bias in the included papers. A meta-analysis was performed using RevMan 5.3 software.ResultsA total of 13 RCTs were eligible for inclusion, including 2,773 patients (1,378 and 1,395 cases in the NaPTab and PEGL groups, respectively). Meta-analysis revealed no significant difference in the cleansing quality of the NaPTab and PEGL groups [RR 1.02, 95% CI (0.96–1.08), P = 0.46]. The incidence of nausea was lower in the NaPTab group than in the PEGL group [RR 0.67, 95% CI (0.58–0.76), p &lt; 0.00001]. Patients rated the taste of NaPTab higher than PEGL [RR 1.33, 95% CI (1.26–1.40), P &lt; 0.00001]. Willingness to repeat the treatment was also higher in the NaPTab group than in the PEGL group [RR 1.52, 95% CI (1.28–1.80), P &lt; 0.00001]. Both serum potassium and serum calcium decreased in both groups after the preparation; however, meta-analysis revealed that both minerals decreased more in the NaPTab group than in the PEGL group [MD = 0.38, 95% CI (0.13–0.62), P = 0.006 for serum potassium and MD = 0.41, 95% CI (0.04–0.77), P = 0.03 for serum calcium]. Meanwhile, serum phosphorus increased in both groups after the preparation; however, levels increased more in the NaPTab group than in the PEGL group [MD 4.51, (95% CI 2.9–6.11), P &lt; 0.00001].ConclusionsWhile NaP tablets and PEGL were shown to have a similar cleaning effect before colonoscopy, NaP tablets had improved patient tolerance. However, NaP tablets had a strong effect on serum potassium, calcium, and phosphorus levels. For patients with low potassium, low calcium, and renal insufficiency, NaP tablets should be prescribed with caution. For those at high-risk for acute phosphate nephropathy, NaP tablets should be avoided. Given the low number and quality of included studies, these conclusions will require additional verification by large high-quality studies.Systematic review registration10.37766/inplasy2023.5.0013, identifier: NPLASY202350013.
Coptischinensis Franch root rot infection disrupts microecological balance of rhizosphere soil and endophytic microbiomes
Authors: Tang Tao , Wang Fanfan , Fang Guobin , Mao Ting , Guo Jie , Kuang Hui , Sun Guangzhong , Guo Xiaoliang , Duan Yuanyuan , You Jingmao 
Published: May 2023

IntroductionThe ecological balance of the plant microbiome, as a barrier against pathogens, is very important for host health. Coptis chinensis is one of the important medicinal plants in China. In recent years, Illumina Miseq high-throughput sequencing technology was frequently used to analyze root rot pathogens and the effects of root rot on rhizosphere microorganisms of C. chinensis. But the effects of root rot infection on rhizosphere microecological balance of C. chinensis have received little attention.MethodsIn this study, Illumina Miseq high-throughput sequencing technology was applied to analyze the impact on microbial composition and diversity of C. chinensis by root rot.ResultsThe results showed that root rot infection had significant impact on bacterial α-diversity in rhizome samples, but had no significant effect on that in leaf samples and rhizosphere soil samples, while root rot infection exhibited significant impact on the fungal α-diversity in leaf samples and rhizosphere soil samples, and no significant impact on that in rhizome samples. PCoA analysis showed that the root rot infection had a greater impact on the fungal community structure in the rhizosphere soil, rhizome, and leaf samples of C. chinensis than on the bacterial community structure. Root rot infection destroyed the microecological balance of the original microbiomes in the rhizosphere soil, rhizome, and leaf samples of C. chinensis, which may also be one of the reasons for the serious root rot of C. chinensis.DiscussionIn conclusion, our findings suggested that root rot infection with C. chinensis disrupts microecological balance of rhizosphere soil and endophytic microbiomes. The results of this study can provide theoretical basis for the prevention and control of C. chinensis root rot by microecological regulation.
Monosomes buffer translational stress to allow for active ribosome elongation
Authors: Schieweck Rico , Ciccopiedi Giuliana , Klau Kenneth , Popper Bastian 
Published: May 2023

Introduction: The synthesis of proteins is a fundamental process in the life-span of all cells. The activation of ribosomes on transcripts is the starting signal for elongation and, in turn, the translation of an mRNA. Thereby, most mRNAs circulate between single (monosomes) and multi ribosomal particles (polysomes), a process that defines their translational activity. The interplay between monosomes and polysomes is thought to crucially impact translation rate. How monosomes and polysomes are balanced during stress remains, however, elusive.Methods: Here, we set out to investigate the monosome and polysome levels as well as their kinetics under different translational stress conditions including mTOR inhibition, downregulation of the eukaryotic elongation factor 2 (eEF2) and amino acid depletion.Results: By using a timed ribosome runoff approach in combination with polysome profiling, we found that the used translational stressors show very distinct effects on translation. However, they all had in common that the activity of monosomes was preferentially affected. This adaptation seems to be needed for sufficient translation elongation. Even under harsh conditions such as amino acid starvation, we detected active polysomes while monosomes were mostly inactive. Hence, it is plausible that cells compensate the reduced availability of essential factors during stress by adapting the levels of active monosomes to favor sufficient elongation.Discussion: These results suggest that monosome and polysome levels are balanced under stress conditions. Together, our data argue for the existence of translational plasticity that ensure sufficient protein synthesis under stress conditions, a process that is necessary for cell survival and recovery.
Altered gut microbiota in older adults with mild cognitive impairment: a case-control study
Authors: Fan Kang-Chen , Lin Chen-Ching , Liu Yi-Chien , Chao Yi-Ping , Lai Yen-Jun , Chiu Yen-Ling , Chuang Yi-Fang 
Published: May 2023

IntroductionThe microbiota-gut-brain axis is implicated in Alzheimer’s disease. Gut microbiota alterations in mild cognitive impairment (MCI) are inconsistent and remain to be understood. This study aims to investigate the gut microbial composition associated with MCI, cognitive functions, and structural brain differences.MethodsA nested case-control study was conducted in a community-based prospective cohort where detailed cognitive functions and structural brain images were collected. Thirty-one individuals with MCI were matched to sixty-five cognitively normal controls by age strata, gender, and urban/rural area. Fecal samples were examined using 16S ribosomal RNA (rRNA) V3–V4 sequencing. Compositional differences between the two groups were identified and correlated with the cognitive functions and volumes/thickness of brain structures.ResultsThere was no significant difference in alpha and beta diversity between MCIs and cognitively normal older adults. However, the abundance of the genus Ruminococcus, Butyricimonas, and Oxalobacter decreased in MCI patients, while an increased abundance of nine other genera, such as Flavonifractor, were found in MCIs. Altered genera discriminated MCI patients well from controls (AUC = 84.0%) and were associated with attention and executive function.ConclusionThis study provides insights into the role of gut microbiota in the neurodegenerative process.
The ANeED study – ambroxol in new and early dementia with Lewy bodies (DLB): protocol for a phase IIa multicentre, randomised, double-blinded and placebo-controlled trial
Authors: Chwiszczuk Luiza Jadwiga , Breitve Monica Haraldseid , Kirsebom Bjørn-Eivind Bordewick , Selnes Per , Fløvig John Chr. , Knapskog Anne-Brita , Skogseth Ragnhild E. , Hubbers Jessica , Holst-Larsen Elin , Rongve Arvid 
Published: May 2023

BackgroundCurrently, there are no disease-modifying pharmacological treatment options for dementia with Lewy bodies (DLB). The hallmark of DLB is pathological alpha-synuclein (aS) deposition. There are growing amounts of data suggesting that reduced aS clearance is caused by failure in endolysosomal and authophagic pathways, as well as and glucocerebrosidase (GCase) dysfunction and mutations in the GCase gene (GBA). The population’s studies demonstrated that the incidence of GBA mutations is higher among Parkinson’s disease (PD) patients, and carriers of such mutations have a higher risk of developing PD. The incidence of GBA mutations is even higher in DLB and a genome-wide association study (GWAS) confirmed the correlation between GBA mutations and DLB. In vivo experiments have shown that ambroxol (ABX) may increase GCase activity and GCase levels and therefore enhance aS autophagy-lysosome degradation pathways. Moreover, there is an emerging hypothesis that ABX may have an effect as a DLB modifying drug. The aims of the study “Ambroxol in new and early Dementia with Lewy Bodies (ANeED) are to investigate the tolerability, safety and effects of ABX in patients with DLB.MethodsThis is a multicentre, phase IIa, double-blinded, randomised and placebo-controlled clinical trial, using a parallel arm design for 18 months’ follow-up. The allocation ratio is 1:1 (treatment:placebo).DiscussionThe ANeED study is an ongoing clinical drug trial with ABX. The unique, but not fully understood mechanism of ABX on the enhancement of lysosomal aS clearance may be promising as a possible modifying treatment in DLB.Trial RegistrationThe clinical trial is registered in the international trials register – clinicaltrials.com (NCT0458825) and nationally at the Current Research Information System in Norway (CRISTIN 2235504).
Functional and technical outcomes in acute ischemic stroke patients with hyperdense middle cerebral artery sign treated with endovascular thrombectomy
Authors: Chen Yimin , Diana Francesco , Mofatteh Mohammad , Zhou Sijie , Chen Juanmei , Huang Zhou , Wu Weijuan , Yang Yajie , Zeng Zhiyi , Zhang Weijian , Ouyang Ziqi , Nguyen Thanh N. , Yang Shuiquan , Baizabal-Carvallo José Fidel , Liao Xuxing 
Published: May 2023

Background and objectiveThe hyperdense middle cerebral artery sign (HMCAS) is observed in a proportion of patients with acute ischemic stroke (AIS). This sign reflects the presence of an intravascular thrombus rich in red blood cells. Several studies have demonstrated that HMCAS increases the risk of poor outcomes in AIS patients treated with IV thrombolysis or no reperfusion therapy; however, whether HMCAS predicts a poor outcome in patients treated with endovascular thrombectomy (EVT) is less clear. We aimed to evaluate the functional outcome by the modified Rankin scale (mRS) at 90 days and technical challenges in patients with HMCAS undergoing EVT.MethodsWe studied 143 consecutive AIS patients with middle cerebral artery M1 segment or internal carotid artery + M1 occlusions who underwent EVT.ResultsThere were 73 patients (51%) with HMCAS. Patients with HMCAS had a higher frequency of cardioembolic stroke (p = 0.038); otherwise, no other baseline difference was observed. No differences in functional outcomes (mRS) at 90  days (p = 0.698), unfavorable outcomes (mRS &gt; 2) (p = 0.929), frequency of symptomatic intracranial hemorrhage (p = 0.924), and mortality (mRS-6) (p = 0.736) were observed between patients with and without HMCAS. In patients with HMCAS, EVT procedures were 9  min longer, requiring a higher number of passes (p = 0.073); however, optimal recanalization scores (modified thrombolysis in cerebral infarction: 2b-3) were equally achieved by both groups.ConclusionPatients with HMCAS treated with EVT do not have a worse outcome at 3  months compared with no-HMCAS patients. Patients with HMCAS required a greater number of thrombus passes and longer procedure times.
Effects of altered excitation–inhibition imbalance by repetitive transcranial magnetic stimulation for self-limited epilepsy with centrotemporal spikes
Authors: Yang Yujiao , Han Yixian , Wang Jing , Zhou Yongkang , Chen Dong , Wang Mengyang , Li Tianfu 
Published: May 2023

ObjectivesPatients with self-limited epilepsy with centrotemporal spikes (SeLECTS) with electrical status epilepticus in sleep (ESES) have generalized cognitive impairment, yet treatment options are limited. Our study aimed to examine the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) on SeLECTS with ESES. In addition, we applied electroencephalography (EEG) aperiodic components (offset and slope) to investigate the improvement of rTMS on the excitation–inhibition imbalance (E-I imbalance) in the brain of this group of children.MethodsEight SeLECTS patients with ESES were included in this study. Low-frequency rTMS (≤1 Hz) was applied for 10 weekdays in each patient. To assess the clinical efficacy and changes in E-I imbalance, EEG recordings were performed both before and after rTMS. Seizure-reduction rate and spike-wave index (SWI) were measured to investigate the clinical effects of rTMS. The aperiodic offset and slope were calculated to explore the effect of rTMS on E-I imbalance.ResultsFive of the eight patients (62.5%) were seizure-free within 3 months after stimulation, with treatment effects decreasing with longer follow-ups. The SWI decreased significantly at 3 and 6 months after rTMS compared with the baseline (P = 0.0157 and P = 0.0060, respectively). The offset and slope were compared before rTMS and within 3 months after stimulation. The results showed a significant reduction in the offset after stimulation (P &lt; 0.0001). There was a remarkable increase in slope after the stimulation (P &lt; 0.0001).ConclusionPatients achieved favorable outcomes in the first 3 months after rTMS. The ameliorative effect of rTMS on SWI may last up to 6 months. Low-frequency rTMS could reduce firing rates in neuronal populations throughout the brain, which was most pronounced at the site of stimulation. A significant reduction in the slope after rTMS treatment suggested an improvement in the E-I imbalance in the SeLECTS.
Conduction treatment of temporal lobe epilepsy in rats: the dose-effect relationship between current resistance and therapeutic effect
Authors: Zhang Shaohui , Yuan Liu , Liu Chunxiu , Kuang Suhui , Wang Jiaqi , Liang Shuli , Cong Ming 
Published: May 2023

ObjectiveTo investigate the effect of current resistance on therapeutic outcomes, and the mechanism of current conduction treatment in a rat model of temporal lobe epilepsy (TLE).MethodsRats were randomly divided into four groups: normal control, epileptic group, low-resistance conduction (LRC) and high-resistance conduction (HRC) group. The content of glutamate (Glu) and gamma-amino butyric acid (GABA) in the hippocampus was determined using a neurotransmitter analyzer. mRNA and protein expression of interleukin 1β (IL-1β) /IL-1 receptor 1(IL-1R1) and high mobility group protein B1 (HMGB-1)/toll-like receptor-4 (TLR-4) in hippocampal neurons were tested. Video electroencephalogram monitoring was used to record seizures and EEG discharges. Cognitive function in the rats was tested using the Morris water maze.ResultsGlu/GABA ratio in the epileptic control and HRC groups was significant differences from LRC group. The levels of HMGB1/TLR4 and IL-1β/IL-1R1 in the LRC group and normal control group were significantly lower than those in epileptic control group (p &lt; 0.01) and the HRC group. The mRNA levels of HMGB1/TLR4 and IL-1β/IL-1R1 in the LRC group and normal control group were significantly lower than those in epileptic control group. The frequency of total and propagated seizures was lower in the LRC group than in the epileptic control and HRC groups (p &lt; 0.01). The numbers of platform crossings in the LRC group and normal control group were significantly higher than those in the epileptic control and HRC groups in the space exploration experiment.ConclusionCurrent resistance affected seizure control and cognitive protection in rats with TLE treated by current conduction. The lower current resistance, the better seizure control and cognitive protection in rats with TLE treated by current conduction. Glu/GABA, IL-1β/IL-1R1, and HMGB1/TLR-4 may participate in the anti-seizure mechanism of current conduction treatment.
Excess cerebellar granule neurons induced by the absence of p75NTR during development elicit social behavior deficits in mice
Authors: Zanin Juan Pablo , Pandya Mansi A. , Espinoza Diego , Friedman Wilma J. , Shiflett Michael W. 
Published: May 2023

IntroductionRecently, the cerebellum has been implicated with non-motor functions, including cognitive and emotional behavior. Anatomical and functional studies demonstrate bidirectional cerebellar connections with brain regions involved in social cognition. Cerebellar developmental abnormalities and injury are often associated with several psychiatric and mental disorders including autism spectrum disorders and anxiety. The cerebellar granule neurons (CGN) are essential for cerebellar function since they provide sensorimotor, proprioceptive, and contextual information to Purkinje cells to modify behavior in different contexts. Therefore, alterations to the CGN population are likely to compromise cerebellar processing and function. Previously we demonstrated that the p75 neurotrophin receptor (p75NTR) was fundamental for the development of the CGN. In the absence of p75NTR, we observed increased proliferation of the granule cell precursors (GCPs), followed by increased GCP migration toward the internal granule layer. The excess granule cells were incorporated into the cerebellar network, inducing alterations in cerebellar circuit processing.MethodsIn the present study, we used two conditional mouse lines to specifically delete the expression of p75NTR in CGN. In both mouse lines, deletion of the target gene was under the control of the transcription factor Atoh-1 promotor, however, one of the lines was also tamoxifen-inducible.ResultsWe observed a loss of p75NTR expression from the GCPs in all cerebellar lobes. Compared to control animals, both mouse lines exhibited a reduced preference for social interactions when presented with a choice to interact with a mouse or an object. Open-field locomotor behavior and operant reward learning were unaffected in both lines. Lack of preference for social novelty and increased anxiety-related behavior was present in mice with constitutive p75NTR deletion; however, these effects were not present in the tamoxifen-inducible mice with p75NTR deletion that more specifically targeted the GCPs.DiscussionOur findings demonstrate that alterations to CGN development by loss of p75NTR alter social behavior, and contribute to the increasing evidence that the cerebellum plays a role in non-motor-related behaviors, including social behavior.
Eat4Genes: a bioinformatic rational gene targeting app and prototype model for improving human health
Authors: Ford Morgan L. , Cooley Jessica M. , Sripada Veda , Xu Zhengwen , Erickson John S. , Bennett Kristin P. , Crawford Dana R. 
Published: May 2023

Introduction and aimsDietary Rational Gene Targeting (DRGT) is a therapeutic dietary strategy that uses healthy dietary agents to modulate the expression of disease-causing genes back toward the normal. Here we use the DRGT approach to (1) identify human studies assessing gene expression after ingestion of healthy dietary agents with an emphasis on whole foods, and (2) use this data to construct an online dietary guide app prototype toward eventually aiding patients, healthcare providers, community and researchers in treating and preventing numerous health conditions.MethodsWe used the keywords “human”, “gene expression” and separately, 51 different dietary agents with reported health benefits to search GEO, PubMed, Google Scholar, Clinical trials, Cochrane library, and EMBL-EBI databases for related studies. Studies meeting qualifying criteria were assessed for gene modulations. The R-Shiny platform was utilized to construct an interactive app called “Eat4Genes”.ResultsFifty-one human ingestion studies (37 whole food related) and 96 key risk genes were identified. Human gene expression studies were found for 18 of 41 searched whole foods or extracts. App construction included the option to select either specific conditions/diseases or genes followed by food guide suggestions, key target genes, data sources and links, dietary suggestion rankings, bar chart or bubble chart visualization, optional full report, and nutrient categories. We also present user scenarios from physician and researcher perspectives.ConclusionIn conclusion, an interactive dietary guide app prototype has been constructed as a first step towards eventually translating our DRGT strategy into an innovative, low-cost, healthy, and readily translatable public resource to improve health.