bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral antibiotics relieve allergic asthma in post-weaning mice via reducing iNKT cells and function of ADRB2
Authors: Li Na , Chen Jie , Xie Sitao , Zhang Meng , Shi Tianyun , He Yanchao , Jie Zhijun , Su Xiao
Published: October 2022

The role of normal gut microbiota in asthma or ovalbumin (OVA)-induced asthma tolerance (OT) remains unclear. Here, we established mouse models of asthma and OT followed by 2 weeks of antibiotic treatment, to clear the gut microbiota. Antibiotic treatment was found to alleviate allergic asthma accompanied with a reduction of invariant natural killer (iNKT) cells. By RNA-seq analysis, we found that β-adrenergic receptor (ADRB) genes, including Adrb1, Adrb2, and Adrb3, were downregulated in asthmatic lungs, but these changes were reversed in OT lungs. Moreover, Adrb2 and Adrb3 were significantly upregulated in asthmatic lungs after antibiotic treatment. Surprisingly, blocking ADRB with propranolol relieved allergic asthma while reducing T helper 2 (Th2) and Treg cell numbers. Further analyses using flow cytometry and immunofluorescence showed that the protein expression level of ADRB2 was higher in asthmatic lungs than that in the control and OT lungs. Notably, dendritic cells (DCs), especially the ADRB2+ DCs, were increased in asthmatic lungs compared to that in the control and OT lungs. In addition, ADRB2+ DCs were significantly reduced following the administration of the ADRB2-specific antagonist ICI118551. Our findings suggest that antibiotic treatment can alleviate OVA-induced allergic asthma via reducing the frequency of iNKT cells and function of ADRB2.
Use of the NIH consensus criteria in cellular and soluble biomarker research in chronic graft-versus-host disease: A systematic review
Authors: Milosevic Emina , Babic Antonija , Iovino Lorenzo , Markovic Milos , Grce Magdalena , Greinix Hildegard
Published: October 2022

Objectives

Chronic graft-versus-host disease (cGvHD) is the most frequent cause of late non-relapse mortality after allogeneic haematopoietic stem cell transplantation (alloHCT). Nevertheless, established biomarkers of cGvHD are still missing. The National Institutes of Health (NIH) Consensus Development Project on Criteria for Clinical Trials in cGvHD provided recommendations for biomarker research. We evaluated to which extent studies on cellular and soluble biomarkers in cGvHD published in the last 10 years complied with these recommendations. Also, we highlight the most promising biomarker candidates, verified in independent cohorts and/or repeatedly identified by separate studies.

Methods

We searched Medline and EMBASE for “cGvHD”, “biomarkers”, “soluble” and “cells” as MeSH terms or emtree subject headings, and their variations on July 28th, 2021, limited to human subjects, English language and last ten years. Reviews, case reports, conference abstracts and single nucleotide polymorphism studies were excluded. Criteria based on the set of recommendations from the NIH group for biomarker research in cGvHD were used for scoring and ranking the references.

Results

A total of 91 references encompassing 15,089 participants were included, 54 prospective, 17 retrospective, 18 cross-sectional, and 2 studies included both prospective and retrospective cohorts. Thirty-five papers included time-matched controls without cGvHD and 20 studies did not have any control subjects. Only 9 studies were randomized, and 8 were multicentric. Test and verification cohorts were included in 11 studies. Predominantly, diagnostic biomarkers were explored (n=54). Assigned scores ranged from 5-34. None of the studies fulfilled all 24 criteria (48 points). Nevertheless, the scores improved during the last years. Three cell subsets (CXCR3+CD56bright NK cells, CD19+CD21low and BAFF/CD19+ B cells) and several soluble factors (BAFF, IL-15, CD163, DKK3, CXCL10 and the panel of ST2, CXCL9, MMP3 and OPN) had the highest potential as diagnostic and/or prognostic biomarkers in cGvHD.

Conclusion

Despite several limitations of this review (limited applicability for paediatric population, definition of verification, missing data on comorbidities), we identified promising candidate biomarkers for further evaluation in multicentre collaborative studies. This review confirms the importance of the NIH consensus group criteria for improving the quality and reproducibility of cGvHD biomarker research.
MUC22, HLA-A, and HLA-DOB variants and COVID-19 in resilient super-agers from Brazil
Authors: Castelli Erick C. , de Castro Mateus V. , Naslavsky Michel S. , Scliar Marilia O. , Silva Nayane S. B. , Pereira Raphaela N. , Ciriaco Viviane A. O. , Castro Camila F. B. , Mendes-Junior Celso T. , Silveira Etiele de S. , de Oliveira Iuri M. , Antonio Eduardo C. , Vieira Gustavo F. , Meyer Diogo , Nunes Kelly , Matos Larissa R. B. , Silva Monize V. R. , Wang Jaqueline Y. T. , Esposito Joyce , Cória Vivian R. , Magawa Jhosiene Y. , Santos Keity S. , Cunha-Neto Edecio , Kalil Jorge , Bortolin Raul H. , Hirata Mário Hiroyuki , Dell’Aquila Luiz P. , Razuk-Filho Alvaro , Batista-Júnior Pedro B. , Duarte-Neto Amaro N. , Dolhnikoff Marisa , Saldiva Paulo H. N. , Passos-Bueno Maria Rita , Zatz Mayana
Published: October 2022

Background

Although aging correlates with a worse prognosis for Covid-19, super elderly still unvaccinated individuals presenting mild or no symptoms have been reported worldwide. Most of the reported genetic variants responsible for increased disease susceptibility are associated with immune response, involving type I IFN immunity and modulation; HLA cluster genes; inflammasome activation; genes of interleukins; and chemokines receptors. On the other hand, little is known about the resistance mechanisms against SARS-CoV-2 infection. Here, we addressed polymorphisms in the MHC region associated with Covid-19 outcome in super elderly resilient patients as compared to younger patients with a severe outcome.

Methods

SARS-CoV-2 infection was confirmed by RT-PCR test. Aiming to identify candidate genes associated with host resistance, we investigated 87 individuals older than 90 years who recovered from Covid-19 with mild symptoms or who remained asymptomatic following positive test for SARS-CoV-2 as compared to 55 individuals younger than 60 years who had a severe disease or died due to Covid-19, as well as to the general elderly population from the same city. Whole-exome sequencing and an in-depth analysis of the MHC region was performed. All samples were collected in early 2020 and before the local vaccination programs started.

Results

We found that the resilient super elderly group displayed a higher frequency of some missense variants in the MUC22 gene (a member of the mucins’ family) as one of the strongest signals in the MHC region as compared to the severe Covid-19 group and the general elderly control population. For example, the missense variant rs62399430 at MUC22 is two times more frequent among the resilient super elderly (p = 0.00002, OR = 2.24).

Conclusion

Since the pro-inflammatory basal state in the elderly may enhance the susceptibility to severe Covid-19, we hypothesized that MUC22 might play an important protective role against severe Covid-19, by reducing overactive immune responses in the senior population.
Response of the metabolic and autophagy pathways in Mytilus under starvation
Authors: Xie Bing , Chen Chuan-yue , Zhang Xiaolin , Li Si-yuan , Gu Zhong-qi , Huang Ji , He Jian-yu , Qi Peng-zhi , Guo Bao-ying , Liao Zhi , Yan Xiaojun
Published: October 2022

Being an industrially valuable species of bivalve, Mytilus is widespread in the area around the eastern coast of China. Starvation is an environmental stress that mussels often encounter in their growth. However, few report carried out on the physiological and biochemical response and molecular regulation and adaptation mechanism of mussels under starvation. To illustrate the molecular mechanism of hosts of Mytilus to starvation, the gill transcriptome was used for analysis before and after 9 days of starvation in Mytilus using the Illumina/HiSeq-2000 deep sequencing platform, accompanied by the study of differentially expressed genes (DEGs). In total, 42.137 GB of clean data were obtained from six sample libraries, the average amount of clean data of each sample is 7.023 GB, and 58,540 unigenes that average 780 bp in length were assembled. Unigenes were illustrated by commenting them against the NR, Swiss-Prot, Pfam, String, GO and KEGG databases. After 9 days of starvation, 2,188 and 2,672 genes were determined to be significantly up- or down-regulated expression genes, separately. Amongst, 4,860 genes were associated with 260 pathways, contains vital enrichment pathways, such as “Metabolic”, “PI3K-Akt signaling pathway”, “Phagosome”, “Apoptosis” and “Lysosome”. In inclusion, autophagy cells were investigated by an electron microscopy, alongside further observations of the expression of autophagy-related genes in gill tissue before and after starvation. The data indicates that the amount of autophagosomes increased and found that atg2, atg6 and atg13 were significantly up-regulated. These results indicated that Mytilus may use autophagy to cope with their damage after starvation. With our research results, we have contributed to a deeper understanding of the role of the molecular mechanisms of immune defence in Mytilus under environmental stress, which has given insights into mussel breeding and the understanding of the molecular mechanisms of Mytilus immune system.
Biochemical and genomic identification of novel biomarkers in progressive sarcoidosis: HBEGF, eNAMPT, and ANG-2
Authors: Casanova Nancy G. , Reyes-Hernon Vivian , Gregory Taylor , Sun Belinda , Bermudez Tadeo , Hufford Matthew K. , Oita Radu C. , Camp Sara M. , Hernandez-Molina Gabriela , Serrano Jorge Rojas , Sun Xiaoguang , Fimbres Jocelyn , Mirsaeidi Mehdi , Sammani Saad , Bime Christian , Garcia Joe G. N.
Published: October 2022

Background

Progressive pulmonary fibrosis is a serious complication in subjects with sarcoidosis. The absence of reliable, non-invasive biomarkers that detect early progression exacerbates the difficulty in predicting sarcoidosis severity. To potentially address this unmet need, we evaluated a panel of markers for an association with sarcoidosis progression (HBEGF, NAMPT, IL1-RA, IL-6, IL-8, ANG-2). This panel encompasses proteins related to inflammation, vascular injury, cell proliferation, and fibroblast mitogenesis processes.

Methods

Plasma biomarker levels and biomarker protein expression in lung and lymph nodes tissues (immunohistochemical studies) from sarcoidosis subjects with limited disease and progressive (complicated) sarcoidosis were performed. Gene expression of the protein-coding genes included in this panel was analyzed using RNAseq in sarcoidosis granulomatous tissues from lung and lymph nodes.

Results

Except for IL-8, plasma levels of each biomarker—eNAMPT, IL-1RA, IL-6, ANG-2, and HBEGF—were significantly elevated in sarcoidosis subjects compared to controls. In addition, plasma levels of HBEGF were elevated in complicated sarcoidosis, while eNAMPT and ANG-2 were observed to serve as markers of lung fibrosis in a subgroup of complicated sarcoidosis. Genomic studies corroborated HBEGF and NAMPT among the top dysregulated genes and identified cytokine-related and fibrotic pathways in lung granulomatous tissues from sarcoidosis.

Conclusion

These findings suggest HBEGF, eNAMPT, and ANG-2 may serve as potential novel indicators of the clinical severity of sarcoidosis disease.
The prebiotic properties of polysaccharides obtained by differentiated deproteinization methods from Flos Sophorae Immaturus on Lactobacillus fermentum
Authors: Zhong Wenting , Yang Chunmiao , Zhang Yongze , Yang Dongsheng
Published: October 2022

The polysaccharides derived from various deproteinization methods were prepared from Flos Sophorae Immaturus (FSI) to investigate the prebiotic efficacy of Lactobacillus fermentum (L.f ). The implications of polysaccharides from FSI (PFSI) gained after purification performed by non-deproteinization and different deproteinization processes (Savage method, papain method, and TCA method) via one-factor optimization were firstly investigated for the influences on the growth of L.f. The utilization of carbohydrate sources and the synthesis of protein and lactate during its growth were analyzed, as well as the variations of LDH, SOD, and GSH- Px enzyme dynamics. The results showed that the one-factor optimization of the deproteinization process with the protein removal rate and polysaccharide retention rate as the indexes led to the optimal methods of the Sevage method with 5 elution times, papain method with 80 U/mL concentration, and TCA method with 2.5 ratio, respectively. In addition, the PFSI obtained with or without deproteinization purification had a certain effect on promoting L.f proliferation. Moreover, the PFSI gained by the third deproteinization purification, at a concentration of 10 g/L, significantly elevated L.f biomass and growth rate compared with the blank control, and the utilization of reducing sugars and the synthesis of protein and lactic acid were higher than the control (P < 0.05); improved LDH, SOD, and GSH-Px activity in L.f (P < 0.05), and the TCA method could be effectively applied to eliminate the proteins affecting FSI in probiotics, and PFSI may be a potentially beneficial prebiotic and intestinal reinforcer.
Monitoring peroxisome dynamics using enhanced green fluorescent protein labeling in Alternaria alternata
Authors: Lu Ziqi , Guo Jian , Li Qiang , Han Yatao , Zhang Zhen , Hao Zhongna , Wang Yanli , Sun Guochang , Wang Jiaoyu , Li Ling
Published: October 2022

Brown leaf spot on tobacco is a serious fungal disease caused byAlternaria alternata. Peroxisomes are organelles playing an important role in the development and infection of plant pathogenic fungi. But, until now, there is no report on the peroxisome dynamics during the conidia germination ofA. alternata. To evaluate the roles of peroxisome in the development of the fungus, in the present work, an enhanced green fluorescent protein (eGFP) cassette tagged with peroxisome targeting signal 2 (PTS2) was integrated intoA. alternatato label the organelles, and an eGFP cassette carrying a nuclear located signal (NLS) was performed parallelly. The transformants containing the fusions emitted fluorescence in punctate patterns. The fluorescence of eGFP-PTS2 was distributed exactly in the peroxisomes while those of eGFP-NLS were located in the nucleus. TypicalAaGB transformants were selected to be investigated for the peroxisome dynamics. The results showed that during spore germination, the number of peroxisomes in the spores decreased gradually, but increased in the germ tubes. In addition, when the transformants were cultured on lipid media, the numbers of peroxisomes increased significantly, and in a larger portion, present in striped shapes. These findings give some clues for understanding the peroxisomal functions in the development ofA. alternata.
Advances in the differential molecular diagnosis of vesicular disease pathogens in swine
Authors: Chen Wenxian , Wang Weijun , Wang Xinyan , Li Zhaoyao , Wu Keke , Li Xiaowen , Li Yuwan , Yi Lin , Zhao Mingqiu , Ding Hongxing , Fan Shuangqi , Chen Jinding
Published: October 2022

Foot-and-mouth disease virus (FMDV), Senecavirus A (SVA) and swine vesicular disease virus (SVDV) are members of the family Picornaviridae, which can cause similar symptoms - vesicular lesions in the tissues of the mouth, nose, feet, skin and mucous membrane of animals. Rapid and accurate diagnosis of these viruses allows for control measures to prevent the spread of these diseases. Reverse transcription-polymerase chain reaction (RT-PCR) and real-time RT-PCR are traditional and reliable methods for pathogen detection, while their amplification reaction requires a thermocycler. Isothermal amplification methods including loop-mediated isothermal amplification and recombinase polymerase amplification developed in recent years are simple, rapid and do not require specialized equipment, allowing for point of care diagnostics. Luminex technology allows for simultaneous detection of multiple pathogens. CRISPR-Cas diagnostic systems also emerging nucleic acid detection technologies which are very sensitivity and specificity. In this paper, various nucleic acid detection methods aimed at vesicular disease pathogens in swine (including FMDV, SVA and SVDV) are summarized.
Antimicrobial activity of cationic antimicrobial peptides against stationary phase bacteria
Authors: Rodríguez-Rojas Alexandro , Rolff Jens
Published: October 2022

Antimicrobial peptides (AMPs) are ancient antimicrobial weapons used by multicellular organisms as components of their innate immune defenses. Because of the antibiotic crisis, AMPs have also become candidates for developing new drugs. Here, we show that five different AMPs of different classes are effective against non-dividing Escherichia coli and Staphylococcus aureus. By comparison, three conventional antibiotics from the main three classes of antibiotics poorly kill non-dividing bacteria at clinically relevant doses. The killing of fast-growing bacteria by AMPs is faster than that of slow-dividing bacteria and, in some cases, without any difference. Still, non-dividing bacteria are effectively killed over time. Our results point to a general property of AMPs, which might explain why selection has favored AMPs in the evolution of metazoan immune systems. The ability to kill non-dividing cells is another reason that makes AMPs exciting candidates for drug development.
Reduction of kinesin I heavy chain decreases tau hyperphosphorylation, aggregation, and memory impairment in Alzheimer’s disease and tauopathy models
Authors: Selvarasu Karthikeyan , Singh Abhay Kumar , Iyaswamy Ashok , Gopalkrishnashetty Sreenivasmurthy Sravan , Krishnamoorthi Senthilkumar , Bera Amal Kanti , Huang Jian-Dong , Durairajan Siva Sundara Kumar
Published: October 2022

Many neurodegenerative diseases, such as Alzheimer’s disease (AD) and frontotemporal dementia with Parkinsonism linked to chromosome 17, are characterized by tau pathology. Numerous motor proteins, many of which are involved in synaptic transmission, mediate transport in neurons. Dysfunction in motor protein-mediated neuronal transport mechanisms occurs in several neurodegenerative disorders but remains understudied in AD. Kinesins are the most important molecular motor proteins required for microtubule-dependent transport in neurons, and kinesin-1 is crucial for neuronal transport among all kinesins. Although kinesin-1 is required for normal neuronal functions, the dysfunction of these motor domains leading to neurodegenerative diseases is not fully understood. Here, we reported that the kinesin-I heavy chain (KIF5B), a key molecular motor protein, is involved in tau homeostasis in AD cells and animal models. We found that the levels of KIF5B in P301S tau mice are high. We also found that the knockdown and knockout (KO) of KIFf5B significantly decreased the tau stability, and overexpression of KIF5B in KIF5B-KO cells significantly increased the expression of phosphorylated and total tau levels. This suggested that KIF5B might prevent tau accumulation. By conducting experiments on P301S tau mice, we showed that partially reducing KIF5B levels can reduce hyperphosphorylation of the human tau protein, formation of insoluble aggregates, and memory impairment. Collectively, our results suggested that decreasing KIF5B levels is sufficient to prevent and/or slow down abnormal tau behavior of AD and other tauopathies.
Abnormal dynamic functional network connectivity in male obstructive sleep apnea with mild cognitive impairment: A data-driven functional magnetic resonance imaging study
Authors: Li Haijun , Li Lan , Li Kunyao , Li Panmei , Xie Wei , Zeng Yaping , Kong Linghong , Long Ting , Huang Ling , Liu Xiang , Shu Yongqiang , Zeng Li , Peng Dechang
Published: October 2022

Objective

The purpose of this study was to investigate the dynamic functional network connectivity (FNC) and its relationship with cognitive function in obstructive sleep apnea (OSA) patients from normal cognition (OSA-NC) to mild cognitive impairment (OSA-MCI).

Materials and methods

Eighty-two male OSA patients and 48 male healthy controls (HC) were included in this study. OSA patients were classified to OSA-MCI (n = 41) and OSA-NC (n = 41) based on cognitive assessments. The independent component analysis was used to determine resting-state functional networks. Then, a sliding-window approach was used to construct the dynamic FNC, and differences in temporal properties of dynamic FNC and functional connectivity strength were compared between OSA patients and the HC. Furthermore, the relationship between temporal properties and clinical assessments were analyzed in OSA patients.

Results

Two different connectivity states were identified, namely, State I with stronger connectivity and lower frequency, and State II with lower connectivity and relatively higher frequency. Compared to HC, OSA patients had a longer mean dwell time and higher fractional window in stronger connectivity State I, and opposite result were found in State II, which was mainly reflected in OSA-MCI patients. The number of transitions was an increasing trend and positively correlated with cognitive assessment in OSA-MCI patients. Compared with HC, OSA patients showed extensive abnormal functional connectivity in stronger connected State I and less reduced functional connectivity in lower connected State II, which were mainly located in the salience network, default mode network, and executive control network.

Conclusion

Our study found that OSA patients showed abnormal dynamic FNC properties, which was a continuous trend from HC, and OSA-NC to OSA-MCI, and OSA patients showed abnormal dynamic functional connectivity strength. The number of transformations was associated with cognitive impairment in OSA-MCI patients, which may provide new insights into the neural mechanisms in OSA patients.
Analysis of electro-chemical RAM synaptic array for energy-efficient weight update
Authors: Kang Heebum , Kim Nayeon , Jeon Seonuk , Kim Hyun Wook , Hong Eunryeong , Kim Seyoung , Woo Jiyong
Published: October 2022

While electro-chemical RAM (ECRAM)-based cross-point synaptic arrays are considered to be promising candidates for energy-efficient neural network computational hardware, array-level analyses to achieve energy-efficient update operations have not yet been performed. In this work, we fabricated CuOx/HfOx/WOx ECRAM arrays and demonstrated linear and symmetrical weight update capabilities in both fully parallel and sequential update operations. Based on the experimental measurements, we showed that the source-drain leakage current (ISD) through the unselected ECRAM cells and resultant energy consumption—which had been neglected thus far—contributed a large portion to the total update energy. We showed that both device engineering to reduce ISD and the selection of an update scheme—for example, column-by-column—that avoided ISD intervention via unselected cells were key to enable energy-efficient neuromorphic computing.
Estimation of knee joint movement using single-channel sEMG signals with a feature-guided convolutional neural network
Authors: Zhang Song , Lu Jiewei , Huo Weiguang , Yu Ningbo , Han Jianda
Published: October 2022

Estimating human motion intention, such as intent joint torque and movement, plays a crucial role in assistive robotics for ensuring efficient and safe human-robot interaction. For coupled human-robot systems, surface electromyography (sEMG) signal has been proven as an effective means for estimating human's intended movements. Usually, joint movement estimation uses sEMG signals measured from multiple muscles and needs many sEMG sensors placed on the human body, which may cause discomfort or result in mechanical/signal interference from wearable robots/environment during long-term routine use. Although the muscle synergy principle implies that it is possible to estimate human motion using sEMG signals from even one signal muscle, few studies investigated the feasibility of continuous motion estimation based on single-channel sEMG. In this study, a feature-guided convolutional neural network (FG-CNN) has been proposed to estimate human knee joint movement using single-channel sEMG. In the proposed FG-CNN, several handcrafted features have been fused into a CNN model to guide CNN feature extraction, and both handcrafted and CNN-extracted features were applied to a regression model, i.e., random forest regression, to estimate knee joint movements. Experiments with 8 healthy subjects were carried out, and sEMG signals measured from 6 muscles, i.e., vastus lateralis, vastus medialis, biceps femoris, semitendinosus, lateral or medial gastrocnemius (LG or MG), were separately evaluated for knee joint estimation using the proposed method. The experimental results demonstrated that the proposed FG-CNN method with single-channel sEMG signals from LG or MG can effectively estimate human knee joint movements. The average correlation coefficient between the measured and the estimated knee joint movements is 0.858 ± 0.085 for LG and 0.856 ± 0.057 for MG. Meanwhile, comparative studies showed that the combined handcrafted-CNN features outperform either the handcrafted features or the CNN features; the performance of the proposed signal-channel sEMG-based FG-CNN method is comparable to those of the traditional multi-channel sEMG-based methods. The outcomes of this study enable the possibility of developing a single-channel sEMG-based human-robot interface for knee joint movement estimation, which can facilitate the routine use of assistive robots.
Hypoglossal nerve stimulation in adolescents with down syndrome and obstructive sleep apnea: A systematic review and meta-analysis
Authors: Liu Pan , Kong Weiguo , Fang Caijing , Zhu Kangxu , Dai Xiaohua , Meng Xiangming
Published: October 2022

Objective

To evaluate the efficacy and adverse effects of hypoglossal nerve stimulation in adolescents with down syndrome and obstructive sleep apnea.

Methods

A systematic search was conducted using PubMed, Web of Science, Embase, and Scopus databases. The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search strategy used a combination of Medical Subject Headings and free words with “OR” and “AND.” Articles were screened to extract data reporting apnea-hypopnea index, quality of life, voltage, follow-up duration, and complications. All included participants were adolescents with down syndrome and obstructive sleep apnea.

Results

A total of 92 articles were identified, of which 9 articles met the inclusion criteria. A total of 106 patients were included. All the studies showed that patients receiving hypoglossal nerve stimulation experienced a significant decrease in apnea-hypopnea index (at least 50%). The pooled AHI was significantly lower in patients following treatment (mean AHI reduction 17.43 events/h, 95% confidence interval 13.98–20.88 events/h, P < 0.001) after 2 case reports were excluded. The pooled OSA-18 were significantly decreased in 88 patients after treatment (mean OSA-18 reduction 1.67, 95% confidence interval 1.27–2.08, P < 0.001) after excluding 5 studies. Four investigations examined the necessity to optimize stimulation voltage for arousal during treatment. The most common complication was pain or discomfort in the tongue or mouth. Most studies had relatively short patient follow-up periods, with the most extended follow-up being 44–58 months.

Conclusion

Hypoglossal nerve stimulation significantly reduces apnea-hypopnea index and improves the quality of life; and thus, could be a potential alternative therapy for obstructive sleep apnea in adolescents with down syndrome. The adolescent's age, potential complications, adverse events, long-term efficacy, and comfort, needs to be considered while performing hypoglossal nerve stimulation.
Oro-mucosal administration of oxytocin using medicated lollipops alters social attention, similar to intranasal and lingual routes: Implications for therapeutic use
Authors: Xu Dan , Li Qin , Zhuang Qian , Zhang Yingying , Yao Shuxia , Zhao Weihua , Kendrick Keith M.
Published: October 2022

A key functional effect of intranasal administration of the neuropeptide oxytocin is on top-down control of social attention. However, an oro-mucosal administration route may be better tolerated for chronic therapeutic use and evidence suggests that some functional effects of oxytocin can be mediated via peripheral routes. The current study investigated if oxytocin administered orally using medicated lollipops can both increase blood oxytocin concentrations and influence social attention and state anxiety. In a randomized, double-blind, clinical trial adult male participants received oral oxytocin (24IU) or placebo 30-min before completing a well-established anti-saccade paradigm which can assess treatment effects on both top-down and bottom-up attention. Oxytocin administration modulated top-down social attentional processing by increasing anti-saccade error rates on both social and non-social stimuli although it only increased response latencies for social cues. Anti-saccade errors were also positively associated with the proportionate increase in plasma oxytocin concentrations. A comparison analysis showed that oral oxytocin administration increased blood concentrations to a similar degree as given by lingual spray, although less than when given intranasally. Importantly, attentional and anxiolytic effects of oxytocin in the anti-saccade task were similar across intranasal, lingual, and oral administration routes. These findings demonstrate that oral administration of oxytocin, similar to via intranasal and lingual routes, can modulate top-down social attention and state anxiety and support its potential for therapeutic use. They also provide further evidence that functional effects of exogenously administered oxytocin can be mediated indirectly either by crossing the blood brain barrier or producing receptor mediated vagal stimulation, as opposed to via direct entry into the brain.
Age-differential sexual dimorphism in CHD8-S62X-mutant mouse behaviors
Authors: Lee Soo Yeon , Kweon Hanseul , Kang Hyojin , Kim Eunjoon
Published: October 2022

Autism spectrum disorders (ASD) are ~4-times more common in males than females, and CHD8 (a chromatin remodeler)-related ASD shows a strong male bias (~4:1), although the underlying mechanism remains unclear. Chd8-mutant mice with a C-terminal protein-truncating mutation (N2373K) display male-preponderant behavioral deficits as juveniles and adults, although whether this also applies to other Chd8 mutations remains unknown. In addition, it remains unclear whether sexually dimorphic phenotypes in Chd8-mutant mice are differentially observed in males and females across different ages. We here generated new Chd8-mutant (knock-in) mice carrying a patient-derived mutation causing an N-terminal and stronger protein truncation (Chd8+/S62X mice) and characterized the mice by behavioral analyses. Juvenile Chd8+/S62X mice displayed male-preponderant autistic-like behaviors; hypoactivity and enhanced mother-seeking/attachment behavior in males but not in females. Adult male and female Chd8+/S62X mice showed largely similar deficits in repetitive and anxiety-like behavioral domains. Therefore, the CHD8-S62X mutation induces ASD-like behaviors in juvenile male mice and adult male and female mice, pointing to an age-differential sexual dimorphism and also distinct sexual dimorphisms in different Chd8 mutations (N2373K and S62X).
Combination effect between gut microbiota and traditional potentially modifiable risk factors for first-ever ischemic stroke in Tujia, Miao and Han populations in China
Authors: Zhang Na , Wang Haoren , Wang Xiaolei , Tian Mengyuan , Tian Yong , Li Qi , Liang Chengcai , Peng Xiaowei , Ding Jian , Wu Xinrui , Tan Hongzhuan
Published: October 2022

China has had explosive growth in ischemic stroke (IS) burden with significant ethnic and geographic disparities. The aim of this study was to explore the possible combination effect between gut microbiota and traditional potentially modifiable risk factors for IS among two ethnic minorities (Tujia and Miao) and the Han population. Herein, we first used the 16 S rRNA sequencing to compare the gut microbial compositions of 82 patients with first-ever IS vs. 82 normal controls (NCs) among Han, Tujia, and Miao people between 1 May 2018 and 30 April 2019, from Xiangxi Tujia and Miao Autonomous Prefecture in China. An additive model was used to study the interaction between traditional risk factors and gut microbiota with R software. Linear discriminant analysis (LDA) and LDA effect size (LEfSe) results showed that the identified key gut microbiota's taxonomic composition varied in different ethnicity between the IS patients and NCs. Furthermore, families Lactobacillaceae, Enterococcaceae, Streptococcaceae, and Enterobacteriaceae were found to be positively correlated with high-risk factors and negatively correlated with preventive factors in the IS patients, but families Ruminococcaceae and Lachnospiraceae were just the opposite in the NCs. There were additive interactions between traditional risk factors (systolic blood pressure, diastolic blood pressure, and high-sensitive C-reactive protein) and family Enterococcaceae for first-ever IS with the attributable proportion due to the interaction was 0.74, 0.71, and 0.85, respectively; and the synergy index was 4.45, 3.78, and 7.01, respectively. This preliminary but promising study showed that the gut microbiota disturbances may potentially interact to IS with different ethnic host's traditional risk factors.
Ras-related protein Rab-20 inhibition alleviates cerebral ischemia/reperfusion injury by inhibiting mitochondrial fission and dysfunction
Authors: Guo Jia , Zhang Lu , Bu Yujie , Li Wenjuan , Hu Jianping , Li Jianxiong
Published: October 2022

Ras-related protein Rab-20 (Rab20) is induced in hypoxia and contributes to hypoxia-induced apoptosis. However, the role and mechanism of Rab20 in cerebral ischemia/reperfusion (I/R) injury need to be elucidated. We established a cerebral I/R injury model in the mice and an oxygen-glucose deprivation/reoxygenation (OGD/R) model in HT22 cells to determine the effects of Rab20 in cerebral I/R injury. Rab20 expression was upregulated in mice after I/R and in HT22 cells after OGD/R. Upregulated Rab20 was mainly located in neurons. Rab20 inhibition significantly alleviated brain infarct volume, neurological deficits, and neuronal apoptosis in mice after I/R. Moreover, Rab20 knockdown significantly ameliorated the OGD/R-induced inhibition of cell viability and apoptotic cell death in HT22 cells. Rab20 knockdown significantly alleviated OGD/R-induced mitochondrial fission by repressing mitochondrial dynamin-related protein 1 (Drp-1) recruitment and increasing Drp-1 (Ser637) phosphorylation and ameliorated mitochondrial dysfunction by reducing the mitochondrial reactive oxygen species (ROS) and cellular calcium accumulation and increasing the mitochondrial membrane potential. In addition, Rab20 knockdown significantly alleviated cytochrome c release from the mitochondria into the cytosol in HT22 cells after OGD/R. Rab20 contributes to cerebral I/R injury by regulating mitochondria-associated apoptosis pathways. Targeting Rab20 may be an attractive strategy for the treatment of cerebral I/R injury.
The advanced lung cancer inflammation index predicts long-term outcomes in patients with hypertension: National health and nutrition examination study, 1999–2014
Authors: Zhang Yanbin , Pan Yuxiong , Tu Jiabin , Liao Lihua , Lin Shuqiong , Chen Kaihong , Ding Shan , Xiao Guitao
Published: October 2022

Background

Malnutrition and systemic inflammation are associated with poor outcomes in patients with hypertension, and the two often coexist. However, few studies have combined nutritional and inflammatory status to assess the prognosis of patients with hypertension. The present study aimed to investigate the association between advanced lung cancer inflammation index (ALI), as a factor assessment the nutritional and inflammatory status, and long-term all-cause mortality of patients with hypertension.

Materials and methods

Data from the National Health and Nutrition Examination Survey (NHANES) 1999–2014 with mortality follow-up through December 31, 2015, were analyzed. A total of 15,681 participants were evaluated. The patients were grouped based on the ALI tertiles as follows: T1 (ALI ≤ 49.41, n = 5,222), T2 (ALI > 49.41 and ≤ 76.29, n = 5,221), and T3 (ALI > 76.29, n = 5,237) groups. Survival curves and Cox regression analysis based on the NHANES recommended weights were used to assess the relationship between nutritional and inflammatory status and long-term all-cause mortality.

Results

Advanced lung cancer inflammation index was significantly associated with long-term all-cause mortality in patients with hypertension. After adjustment for related factors, the T2 [hazard ratio (HR): 0.69, 95% confidence interval (CI): 0.58–0.83; P < 0.001) and T3 (HR: 0.59, 95% CI: 0.47–0.74; P < 0.001) groups were significantly associated with a decreased risk of all-cause mortality compared to the lower ALI level group (T1).

Conclusion

Advanced lung cancer inflammation index was a comprehensive index of nutrition and inflammation and an independent significant prognostic factor in hypertension patients in the American community. Systemic inflammatory and nutritional status assessment and monitoring are essential for the health of hypertensive patients.
Clinicopathological characteristics and loss of mismatch repair protein expression in Chinese upper tract urothelial carcinomas
Authors: Shang Zhi , Jin Shengming , Wang Wenwen , Wei Yu , Gu Chengyuan , Yang Chen , Zhu Yu , Zhu Yao , Shen Yijun , Wu Junlong , Ye Dingwei
Published: October 2022

Expression of DNA mismatch repair (MMR) protein (MLH1, PMS2, MSH2, and MSH6) in upper tract urothelial carcinoma (UTUC) has been explored in Western cohorts, but it is rarely reported in Eastern cohorts. We aimed to assess the loss of MMR protein expression among Chinese UTUC patients and study its clinicopathological implications. We enrolled 175 UTUC patients at our center and tested the expression of MMR proteins by immunohistochemistry. Then, we explored these patients’ clinicopathological characteristics. We found loss of MMR proteins in 19 (10.9%) of 175 patients in our cohort (6 MSH2 and MSH6, 2 MSH6 alone, 6 MSH2 alone, 3 MLH1 and PMS2, and 2 PMS2 alone). Loss of MMR proteins was not a significant prognostic factor of relapse-free survival for these patients. In addition, patients with lower T stage or with bladder cancer history were more likely to have loss of MMR protein expression. At last, two metastatic patients (MSH2 and MSH6 loss; MSH2 loss) with loss of MMR protein experienced tumor recession after several cycles of anti-PD-1 immunotherapy. In conclusion, this is the largest Chinese UTUC cohort study to date that explores the loss of MMR protein expression. The rate of MMR loss observed was comparable to that in the Western UTUC cohort, supporting universal UTUC screening in China. Furthermore, a subset of advanced UTUCs with MMR protein loss are probably immunogenic, for whom single or combined immunotherapy may be potential therapeutic options in the future.
Breast cancer liver metastasis: Pathogenesis and clinical implications
Authors: Liu Cuiwei , Mohan Srivarshini C. , Wei Jielin , Seki Ekihiro , Liu Manran , Basho Reva , Giuliano Armando E. , Zhao Yanxia , Cui Xiaojiang
Published: October 2022

Breast cancer is the most common malignant disease in female patients worldwide and can spread to almost every place in the human body, most frequently metastasizing to lymph nodes, bones, lungs, liver and brain. The liver is a common metastatic location for solid cancers as a whole, and it is also the third most common metastatic site for breast cancer. Breast cancer liver metastasis (BCLM) is a complex process. Although the hepatic microenvironment and liver sinusoidal structure are crucial factors for the initial arrest of breast cancer and progression within the liver, the biological basis of BCLM remains to be elucidated. Importantly, further understanding of the interaction between breast cancer cells and hepatic microenvironment in the liver metastasis of breast cancer will suggest ways for the development of effective therapy and prevention strategies for BCLM. In this review, we provide an overview of the recent advances in the understanding of the molecular mechanisms of the hepatic microenvironment in BCLM formation and discuss current systemic therapies for treating patients with BCLM as well as potential therapeutic development based on the liver microenvironment-associated signaling proteins governing BCLM.
The gut microbiota modulates responses to anti–PD-1 and chemotherapy combination therapy and related adverse events in patients with advanced solid tumors
Authors: Wu Zhaozhen , Zhang Sujie , Li Lingling , Huang Ziwei , Huang Di , Hu Yi
Published: October 2022

Background

Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) have been widely used in treating different malignancies. Several studies have reported that the gut microbiota modulates the response and adverse events (AEs) to ICIs in melanoma, non–small cell lung cancer (NSCLC), renal cell cancer and hepatocellular carcinoma, but data on other cancer types and ICI combination therapy are limited.

Methods

Stool samples were collected from patients with cancer who received anti–PD-1 and chemotherapy combination treatment and were analyzed by fecal metagenomic sequencing. The microbiota diversity and composition were compared between the responder (R) and non-responder (NR) groups and the AE vs. the non-AE (NAE) groups. In addition, associated functional genes and metabolic pathways were identified.

Results

At baseline, the microbiota diversity of the groups was similar, but the genera Parabacteroides, Clostridia bacterium UC5.1_2F7, and Bifidobacterium dentium were enriched in the R group, whereas Bacteroides dorei and 11 species of Nocardia were enriched in the NR group. At 6 weeks, the beta diversity was significantly different between the R and NR groups. Further analysis found that 35 genera, such as Alipes, Parabacteroides, Phascolarctobacterium, Collinsella, Ruminiclostridium, Porphyromonas, and Butyricimonas and several genera of the Fibrobacteraceae family, were frequently distributed in the R group, whereas 17 genera, including Enterococcus, Lachnoclostridium, Hungatella, and Bilophila and several genera of the Pseudonocardiaceae and Beijerinckiaceae families, were more abundant in the NR group. A total of 66 and 52 Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologs (KOs) were significantly enriched in the R and NR groups, respectively. In addition, pathway analysis revealed functional differences in the gut microbacteria in the R group, including the enrichment of anabolic pathways and DNA damage repair (DDR) pathways. Dynamic comparisons of the bacterial composition at baseline, 6 weeks, and 12 weeks showed that the abundance of Weissella significantly increased in the R group at 6 weeks and the abundance of Fusobacterium and Anaerotruncus significantly increased in the NR group at 12 weeks. Linear discriminant analysis effect size analysis indicated that bacteria of Bacteroidetes, especially Bacteroides, were enriched in the NAE group, whereas flora of Firmcutes, such as Faecalibacterium prausnitzii, Bacteroides fragilis, and Ruminococcus lactaris, were enriched in the AE group.

Conclusion

Beta diversity and differences in the gut microbiota modulated AEs and the response to anti–PD-1 blockade combined with chemotherapy, by regulating related anabolic and DDR pathways. Dynamic changes in the intestinal microbiome may predict the efficacy of PD-1 inhibitor–based therapy.
Metformin-induced AMPK activation promotes cisplatin resistance through PINK1/Parkin dependent mitophagy in gastric cancer
Authors: Xiao Yi-Yi , Xiao Jin-Xing , Wang Xiao-Yu , Wang Tao , Qu Xin-Hui , Jiang Li-Ping , Tou Fang-Fang , Chen Zhi-Ping , Han Xiao-Jian
Published: October 2022

Gastric cancer (GC) is one of the most common tumors worldwide, and cisplatin is a standard chemotherapeutic reagent for GC treatment. However, chemoresistance is an inherent challenge which limits its application and effectiveness in clinic. This study aims to investigate the mechanism of metformin-induced cisplatin resistance in GC. Intriguingly, the upregulation of mitophagy markers, mitochondrial fission, autophagy and mitophagosome were observed in SGC-7901/DDP cells compared to those in the SGC-7901 cells. Treatment with metformin significantly increased mitochondrial fission and mitophagy in both AGS and SGC-7901 cells, resulting in decreased ATP production, which unexpectedly protected GC cells against the cytotoxicity of cisplatin. In contrast, application of Chloroquine and 3-methyladenine, two inhibitors of autophagy, significantly alleviated the protective effect of metformin on SGC-7901 and AGS cells against cytotoxicity of cisplatin. Moreover, metformin also stimulated the phosphorylation of AMPK (Thr172) and increased the expression of mitophagy markers including Parkin and PINK1 in the AMPK signaling-dependent manner. Consistently, the cell viability and cell apoptosis assay showed that metformin-induced cisplatin resistance was prevented by knockdown of AMPKα1. Taken together, all data in this study indicate that metformin induced AMPK activation and PINK1/Parkin dependent mitophagy, which may contribute to the progression of cisplatin resistance in GC.
H2B gene family: A prognostic biomarker and correlates with immune infiltration in glioma
Authors: Jia Jingnan , Han Zhaocheng , Wang Xueke , Zheng Xiancheng , Wang Shurui , Cui Yinglin
Published: October 2022

The current prognosis of glioma is unfavorable and effective treatments remain limited. However, bioinformatics has created new opportunities for improving glioma treatment. Research indicates that H2B is involved in the pathological process of cancer. Thus, this study conducted bioinformatic analyses of the H2B gene family to evaluate whether these genes can play a role in predicting prognosis and are associated with immune infiltration. High expression of H2B genes was observed in cholangiocarcinoma, esophageal carcinoma, glioblastoma multiforme (GBM), head and neck squamous cell carcinoma, and other cancers. In addition, a rise in H2B gene expression was correlated with an increase in glioma grade. In the Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA) database and multiple datasets from the Gene Expression Omnibus (GEO), high expression of H2B gene family members predicted poor prognosis of a variety of tumors including glioma. In particular, high H2BC5, H2BC9, H2BC11, and H2BC21 expression was associated with poor glioma prognosis. H2BC9, H2BC11, and H2BC12 expression were also positively correlated with both immune and stromal scores. Enrichment analysis indicated that H2B family genes may be involved in the pathological process of glioma using various pathways including the cell cycle and immune response. H2B-specific siRNAs were used to verify the role of H2BC5, H2BC9, H2BC11, and H2BC21 expression on cell cycle distribution. In summary, H2BC5, H2BC9, H2BC11, and H2BC21 were independent prognostic indicators of glioma, and H2BC9 and H2BC11 may correlate with tumor immunity.