bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous C5 and CD14 inhibition limits inflammation and organ dysfunction in pig polytrauma
Authors: Lupu Ludmila , Horst Klemens , Greven Johannes , Mert Ümit , Ludviksen Judith A.K. , Pettersen Kristin , Lau Corinna , Li Yang , Palmer Annette , Qin Kang , Zhang Xing , Mayer Benjamin , van Griensven Martijn , Huber-Lang Markus , Hildebrand Frank , Mollnes Tom Eirik
Published: August 2022

Dysfunctional complement activation and Toll-like receptor signaling immediately after trauma are associated with development of trauma-induced coagulopathy and multiple organ dysfunction syndrome. We assessed the efficacy of the combined inhibition therapy of complement factor C5 and the TLR co-receptor CD14 on thrombo-inflammation and organ damage in an exploratory 72-h polytrauma porcine model, conducted under standard surgical and intensive care management procedures. Twelve male pigs were subjected to polytrauma, followed by resuscitation (ATLS® guidelines) and operation of the femur fracture (intramedullary nailing technique). The pigs were allocated to combined C5 and CD14 inhibition therapy group (n=4) and control group (n=8). The therapy group received intravenously C5 inhibitor (RA101295) and anti-CD14 antibody (rMil2) 30 min post-trauma. Controls received saline. Combined C5 and CD14 inhibition reduced the blood levels of the terminal complement complex (TCC) by 70% (p=0.004), CRP by 28% (p=0.004), and IL-6 by 52% (p=0.048). The inhibition therapy prevented the platelet consumption by 18% and TAT formation by 77% (p=0.008). Moreover, the norepinephrine requirements in the treated group were reduced by 88%. The inhibition therapy limited the organ damage, thereby reducing the blood lipase values by 50% (p=0.028), LDH by 30% (p=0.004), AST by 33%, and NGAL by 30%. Immunofluorescent analysis of the lung tissue revealed C5b-9 deposition on blood vessels in five from the untreated, and in none of the treated animals. In kidney and liver, the C5b-9 deposition was similarly detected mainly the untreated as compared to the treated animals. Combined C5 and CD14 inhibition limited the inflammatory response, the organ damage, and reduced the catecholamine requirements after experimental polytrauma and might be a promising therapeutic approach.
Mechanism of selenomethionine inhibiting of PDCoV replication in LLC-PK1 cells based on STAT3/miR-125b-5p-1/HK2 signaling
Authors: Ren Zhihua , Ding Ting , He Hongyi , Wei Zhanyong , Shi Riyi , Deng Junliang
Published: August 2022

There are no licensed therapeutics or vaccines available against porcine delta coronavirus (PDCoV) to eliminate its potential for congenital disease. In the absence of effective treatments, it has led to significant economic losses in the swine industry worldwide. Similar to the current coronavirus disease 2019 (COVID-19) pandemic, PDCoV is trans-species transmissible and there is still a large desert for scientific exploration. We have reported that selenomethionine (SeMet) has potent antiviral activity against PDCoV. Here, we systematically investigated the endogenous immune mechanism of SeMet and found that STAT3/miR-125b-5p-1/HK2 signalling is essential for the exertion of SeMet anti-PDCoV replication function. Meanwhile, HK2, a key rate-limiting enzyme of the glycolytic pathway, was able to control PDCoV replication in LLC-PK1 cells, suggesting a strategy for viruses to evade innate immunity using glucose metabolism pathways. Overall, based on the ability of selenomethionine to control PDCoV infection and transmission, we provide a molecular basis for the development of new therapeutic approaches.
Constructing a novel gene signature derived from oxidative stress specific subtypes for predicting survival in stomach adenocarcinoma
Authors: Zhou Renlong , Peng Naixiong , Li Wei
Published: August 2022

Oxidative stress (OS) response is crucial in oncogenesis and progression of tumor. But the potential prognostic importance of OS-related genes (OSRGs) in stomach adenocarcinoma (STAD) lacked comprehensive study. STAD clinical information and transcriptome data were retrieved from the Gene Expression Omnibus and The Cancer Genome Atlas databases. The prognostic OSRGs were filtered via the univariate Cox analysis and OSRG-based molecular subtypes of STAD were developed using consensus clustering. Weighted gene co-expression network analysis (WGCNA) was subsequently conducted to filter molecular subtype-associated gene modules. The prognosis-related genes were screened via univariate and least absolute shrinkage and selection operator Cox regression analysis were used to construct a prognostic risk signature. Finally, a decision tree model and nomogram were developed by integrating risk signature and clinicopathological characteristics to analyze individual STAD patient’s survival. Four OSRG-based molecular subtypes with significant diversity were developed based on 36 prognostic OSRGs for STAD, and an OSRGs-based subtype-specific risk signature with eight genes for prognostic prediction of STAD was built. Survival analysis revealed a strong prognostic performance of the risk signature exhibited in predicting STAD survival. There were significant differences in mutation patterns, chemotherapy sensitivity, clinicopathological characteristics, response to immunotherapy, biological functions, immune microenvironment, immune cell infiltration among different molecular subtypes and risk groups. The risk score and age were verified as independent risk factors for STAD, and a nomogram integrating risk score and age was established, which showed superior predictive performance for STAD prognosis. We developed an OSRG-based molecular subtype and identified a novel risk signature for prognosis prediction, providing a useful tool to facilitate individual treatment for patients with STAD.
Thrombocytopenia in the first trimester predicts adverse pregnancy outcomes in obstetric antiphospholipid syndrome
Authors: Jin Jiayang , Xu Xue , Hou Lei , Hou Yuke , Li Jing , Liang Meiying , Li Chun
Published: August 2022

Background

Thrombocytopenia is a common manifestation of antiphospholipid syndrome (APS), and is a main concern for bleeding on the standard treatment of low dose aspirin (LDA) and low molecular weight heparin (LMWH) in obstetric APS (OAPS).

Objective

This study assesses the possible relationship between thrombocytopenia during the first trimester and adverse pregnancy outcomes (APOs) in OAPS patients.

Methods

A case-control study was conducted at Peking University People’s Hospital, Beijing, China. The clinical, immunologic, and pregnancy outcomes of the OAPS patients were collected. Univariate and multivariate logistic regression analyses were applied to assess the relationship between APOs and thrombocytopenia in the first trimester.

Results

A total of 115 participants were included in the analysis. There were no difference on antepartum and postpartum hemorrhage between the two groups. The gestational age in the thrombocytopenia group was less than that in the control group (34.12 ± 8.44 vs. 37.44 ± 3.81 weeks, p = 0.002). Hypocomplementemia, double aPL positive, and high titers of anti-β2 glycoprotein I were more frequent in APS patients with thrombocytopenia (p < 0.05). Compared to the control group, thrombocytopenia in the first trimester was correlated with SGA (12.12% vs. 31.25%, p = 0.043), premature birth <37 weeks (16.16% vs 43.75%, p = 0.010) and intrauterine fetal death (2.02% vs 12.50%, p = 0.033). Thrombocytopenia in first-trimester independently increased the risk of preterm birth <37 weeks (OR = 5.40, 95% CI: 1.35-21.53, p = 0.02) after adjusting for demographic and laboratory factors. After adding medication adjustments, these factors above become insignificant (p > 0.05). Of note, the number of platelets increased after delivery in 14 thrombocytopenia patients with live fetuses (p = 0.03).

Conclusion

This study demonstrates that thrombocytopenia in the first trimester increases the risks of preterm birth in women with APS. The effective OAPS treatments may improve pregnancy outcomes and not increase the risk of antepartum and postpartum hemorrhage.
Role of released mitochondrial DNA in acute lung injury
Authors: Long Gangyu , Gong Rui , Wang Qian , Zhang Dingyu , Huang Chaolin
Published: August 2022

Acute lung injury(ALI)/acute respiratory distress syndrome(ARDS) is a form of acute-onset hypoxemic respiratory failure characterised by an acute, diffuse, inflammatory lung injury, and increased alveolar-capillary permeability, which is caused by a variety of pulmonary or nonpulmonary insults. Recently, aberrant mitochondria and mitochondrial DNA(mtDNA) level are associated with the development of ALI/ARDS, and plasma mtDNA level shows the potential to be a promising biomarker for clinical diagnosis and evaluation of lung injury severity. In mechanism, the mtDNA and its oxidised form, which are released from impaired mitochondria, play a crucial role in the inflammatory response and histopathological changes in the lung. In this review, we discuss mitochondrial outer membrane permeabilisation (MOMP), mitochondrial permeability transition pore(mPTP), extracellular vesicles (EVs), extracellular traps (ETs), and passive release as the principal mechanisms for the release of mitochondrial DNA into the cytoplasm and extracellular compartments respectively. Further, we explain how the released mtDNA and its oxidised form can induce inflammatory cytokine production and aggravate lung injury through the Toll-like receptor 9(TLR9) signalling, cytosolic cGAS-stimulator of interferon genes (STING) signalling (cGAS-STING) pathway, and inflammasomes activation. Additionally, we propose targeting mtDNA-mediated inflammatory pathways as a novel therapeutic approach for treating ALI/ARDS.
Licensing microgels prolong the immunomodulatory phenotype of mesenchymal stromal cells
Authors: Patrick Matthew D. , Annamalai Ramkumar T.
Published: August 2022

Mesenchymal stromal cells (MSC) are sensors of inflammation, and they exert immunomodulatory properties through the secretion of cytokines and exosomes and direct cell-cell interactions. MSC are routinely used in clinical trials and effectively resolve inflammatory conditions. Nevertheless, inconsistent clinical outcomes necessitate the need for more robust therapeutic phenotypes. The immunomodulatory properties of MSC can be enhanced and protracted by priming (aka licensing) them with IFNγ and TNFα. Yet these enhanced properties rapidly diminish, and prolonged stimulation could tolerize their response. Hence a balanced approach is needed to enhance the therapeutic potential of the MSC for consistent clinical performance. Here, we investigated the concentration-dependent effects of IFNγ and TNFα and developed gelatin-based microgels to sustain a licensed MSC phenotype. We show that IFNγ treatment is more beneficial than TNFα in promoting an immunomodulatory MSC phenotype. We also show that the microgels possess integrin-binding sites to support adipose tissue-derived MSC (AD-MSC) attachment and a net positive charge to sequester the licensing cytokines electrostatically. Microgels are enzymatically degradable, and the rate is dependent on the enzyme concentration and matrix density. Our studies show that one milligram of microgels by dry mass can sequester up to 641 ± 81 ng of IFNγ. Upon enzymatic degradation, microgels exhibited a sustained release of IFNγ that linearly correlated with their degradation rate. The AD-MSC cultured on the IFNγ sequestered microgels displayed efficient licensing potential comparable to or exceeding the effects of bolus IFNγ treatment. When cultured with proinflammatory M1-like macrophages, the AD-MSC-seeded on licensing microgel showed an enhanced immunomodulatory potential compared to untreated AD-MSC and AD-MSC treated with bolus IFNγ treatment. Specifically, the AD-MSC seeded on licensing microgels significantly upregulated Arg1, Mrc1, and Igf1, and downregulated Tnfα in M1-like macrophages compared to other treatment conditions. These licensing microgels are a potent immunomodulatory approach that shows substantial promise in elevating the efficacy of current MSC therapies and may find utility in treating chronic inflammatory conditions.
Identification of individual bottlenose dolphins (Tursiops truncatus) emitters using a cheap wearable acoustic tag
Authors: Gallo Alessandro , Thieffry Aglaé , Boye Martin , Monmasson Kyra , Hausberger Martine , Lemasson Alban
Published: August 2022

Study of animal communication and its potential social role implies associating signals to an emitter. This has been a major limitation in the study of cetacean communication as they produce sounds underwater with no distinctive behavioral signs. Different techniques have been used to identify callers, but all proved to have ethical or practical limitations. Bio-logging technology has recently provided new hopes, but tags developed so far are costly and do not allow sufficiently reliable discrimination between calls made by the tagged individual and those made by the surrounding individuals. We propose a new device developed at reasonable cost while providing reliable recordings. We tested caller identification through recordings of vocal production of a group of captive bottlenose dolphins under controlled and spontaneous contexts. Our device proved to identify callers through visual examination of sonograms and quantitative measures of amplitudes, even if tagged emitters are 0.4 m apart (regardless of body orientations). Although this device is not able to identify emitters in an entire group when all individuals are not equipped, it enables efficient exclusion of individuals who were not the caller, suggesting that identification of a caller would be reliable if all the individuals were equipped. This is to our knowledge the first description of a promising low-cost safe recording device allowing individual identification of emitters for captive dolphins. With some improvements, this device could become an interesting tool to increase our knowledge of dolphin acoustic communication.
Currents shaped the genetic structure of Tridentiger barbatus (Günther 1861) along the Chinese coast
Authors: Wei Jiehong , Liu Min-Yun , Shiao Jen-Chieh , Li Fan , Yang Jinquan , Iizuka Yoshiyuki , Kang Bin , Tseng Ruo-Shan , Shao Huan-Jie , Liao Te-Yu
Published: August 2022

The modern coast of China is characterized by complicated hydrology, which might be a potential factor shaping genetic structure of marine organisms. Tridentiger barbatus is a widespread benthic goby in coastal China whose range expansion might depend on larval dispersal in its spawning season. We explored the genetic structure of T. barbatus and its interrelationships with coastal currents, planktonic larval duration, and Pleistocene climate fluctuations. Genealogies of Cytb, Rh, and RAG1 reveal two lineages in T. barbatus, namely the southern and northern lineages. The southern lineage is distributed through the South China Sea to the South Yellow Sea but is absent from the North Yellow Sea and Bohai Sea. The HYCOM average flow field indicates an eddy between the North and South Yellow Seas, which might cause larval retention and limit dispersal of the southern lineage into the North Yellow Sea and the Bohai Sea. The northern lineage is distributed through the South Yellow Sea to the Bohai Sea but is absent from the South China Sea and East China Sea. The distribution of the northern lineage fits the eastward deflection of the Yellow Sea Coastal Current at the boundary of the East China Sea and South Yellow Sea, which might limit southward larval dispersal of the northern lineage into the East China Sea. We also uncovered two Cytb haplotype groups within the southern lineage, namely groups A and B, whose distributions might be shaped by the northward Taiwan Strait Current. The coincidence between the genetic structure of T. barbatus and the coastal currents and eddies strongly implies significant roles of larval dispersal and current transportation in shaping the genetic structure of T. barbatus. In addition, significant isolation by distance is found in the southern lineage, which coincides with its short planktonic larval duration (20–30 days). The inference on divergence time suggests that the observed lineages and haplotype groups in T. barbatus originated in the Pleistocene glaciations. Therefore, the coastal currents, planktonic larval duration, and historical glacial isolation are proposed as important factors shaping the genetic structure of T. barbatus.
Cellular disturbance and thermal stress response in mussels exposed to synthetic and natural microfibers
Authors: Pittura Lucia , Nardi Alessandro , Cocca Mariacristina , De Falco Francesca , d’Errico Giuseppe , Mazzoli Carola , Mongera Federica , Benedetti Maura , Gorbi Stefania , Avella Maurizio , Regoli Francesco
Published: August 2022

Textile microfibers (MFs) have natural (e.g. cotton, wool and silk) or synthetic origin (e.g. polyester and polyamide), and are increasingly documented in the marine environment. Knowledge on their biological effects in marine organisms is still limited, and virtually unexplored is their capability to modulate the responsiveness toward other stressors, including those of emerging relevance under global changes scenario. With such background, the aims of this study were to i) determine the ingestion and biological effects of MFs, discriminating between synthetic and natural ones, and ii) elucidate the possibility that MFs alter the responsiveness toward additional stressors occurring at a later stage, after exposure. Adult mussels Mytilus galloprovincialis were exposed for 14 days to a high but still environmentally realistic concentration of 50 MFs L-1 of either polyester (618 ± 367 µm length, 13 ± 1 µm diameter), polyamide (566 ± 500 µm length, 11 ± 1 µm in diameter) or cotton (412 ± 342 µm length, 16 ± 4 µm diameter). After the exposure, mussels were left for 7 days to recover at control temperature (23°C) or exposed to a heatwave condition (27°C). At the end of each phase (exposure – recovery – heat stress), MFs ingestion-elimination was evaluated, along with a wide panel of biological responses, including neuro-immune and antioxidant systems alterations, lipid metabolism and onset of cellular damages. Results were elaborated through a Weight of Evidence approach to provide synthetic hazard indices based on both the magnitude and toxicological relevance of observed variations. Beside limited differences in retention and elimination of MFs, biological analyses highlighted disturbance of the immune system and demand of protection toward oxidative insult, particularly evident in mussels exposed to synthetic-MFs. Carry-over effects were observed after 7 days of recovery: organisms that had been previously exposed to MFs showed a higher susceptibility of the neuroendocrine-immune system and lipid metabolism to thermal stress compared to un-exposed mussels. Overall, this study provided evidence of direct cellular effects of MFs, emphasizing differences between synthetic and natural ones, and highlighted their capability to modulate organisms’ susceptibility toward additional stressors, as those predicted for future changes in marine ecosystems.
Evaluation of the biotechnological potential of peptide Cupiennin 1a and analogs
Authors: Araújo Rayssa Oliveira , Leite Michel Lopes , Dutra Thais Tavares Baraviera , Brito da Cunha Nicolau , Rezende Taia Maria Berto , Ramada Marcelo Henrique Soller , Dias Simoni Campos
Published: August 2022

Antimicrobial peptides (AMPs) are components in the innate immune system of various organisms, and many AMPs can be found in poisons from animals such as spiders, scorpions, and snakes. The peptide Cupiennin-1a is present in the venom of the spider Cupiennius salei and belongs to a group of peptides called cupiennins. The peptide demonstrated high cytotoxic activity against mammalian cells; thus, aiming to solve this problem, seven analogs were designed (R1a, R1b, R2b, R3b, R6b, R8b, and R10b) based on the primary structure of the peptide Cupiennin 1a, reducing its size and substituting some amino acid residues. The antimicrobial results showed that all Cupiennin 1a analogs displayed antimicrobial activity against the tested bacterial and fungal strains. Cytotoxicity tests demonstrated a decrease in the cytotoxic effect of the analogs when compared to the peptide Cupiennin-1a. The antitumor activity against breast adenocarcinoma lines was observed for all the peptides, displaying a better effect against the MCF-7 and MDAMB-231 cell lines. The eight peptides have insecticidal potential, and the original peptide and analogs R6b, R8b, and R10b showed better efficiency even at low concentrations. The rational design of the analogs led to new molecules displaying activities against different cell types and reduced cytotoxicity toward healthy mammalian cells when compared to the original peptide, demonstrating that this was an interesting approach for the development of molecules with biotechnological potential.
Probiotic Lactobacilli ameliorate alcohol-induced hepatic damage via gut microbial alteration
Authors: Kim Juseok , Ahn Seong Woo , Kim Joon Yong , Whon Tae Woong , Lim Seul Ki , Ryu Byung Hee , Han Nam Soo , Choi Hak-Jong , Roh Seong Woon , Lee Se Hee
Published: August 2022

Alcoholic liver disease (ALD), which includes fatty liver, cirrhosis, steatosis, fibrosis, and hepatocellular carcinoma, is a global health problem. The probiotic effects of lactic acid bacteria (LAB) are well-known; however, their protective effect against ALD remains unclear. Therefore, in this study, our objective was to assess the protective effects of LAB on ALD. To this end, mice were fed either a normal diet or an alcohol diet for 10 days (to induce ALD) accompanied by vehicle treatment (the NC and AC groups) or kimchi-derived LAB (Lactiplantibacillus plantarum DSR J266 and Levilactobacillus brevis DSR J301, the AL group; or Lacticaseibacillus rhamnosus GG, the AG group). Our results showed that mice in the AC group showed significantly higher serum aspartate aminotransferase and alanine aminotransferase levels than those in the normal diet groups; however, their levels in the AL and AG groups were relatively lower. We also observed that the AL and AG groups showed relatively lower interleukin-6 levels than the AC group. Additionally, AC group showed the accumulation of several fat vesicles in the liver, while the AL and AG groups showed remarkably lower numbers of fat vesicles. The relative abundance of Enterococcus feacalis, which showed association with liver injury, significantly increased in the AC group compared with its levels in the normal diet groups. However, the AG group showed a decreased relative abundance in this regard, confirming that LAB exerted an improvement effect on gut microbial community. These findings suggested that via gut microbiota alteration, the ingestion of LAB can alleviate the ill effects of alcohol consumption, including inflammation, liver damage, gut dysbiosis, and abnormal intestinal nutrient metabolism.
Dynamic alterations in the donkey fecal bacteria community and metabolome characteristics during gestation
Authors: Zhang Zhenwei , Huang Bingjian , Wang Yonghui , Zhan Yandong , Zhu Mingxia , Wang Changfa
Published: August 2022

In donkeys, the gestation period is a dynamic and precisely coordinated process involving systemic and local alterations. Both the gut microbiota and its link with blood metabolites are thought to play significant roles in maintaining maternal health and supporting fetal development during the gestation period. This study was conducted to evaluate gut microbiota changes and the correlation with plasma metabolites in Dezhou donkeys during the gestation period. The donkeys were divided into the four following groups according to their pregnancy stages: the non-pregnant (NP), early stage of pregnancy (P1), middle stage of pregnancy (P2), and late stage of pregnancy (P3) groups. A total of 24 (n = 6 per group) samples of donkey feces and plasma were collected. The results showed that the diversity (Shannon index) of fecal bacteria significantly increased throughout the gestation period. The phyla Spirochaetota and Fibrobacterota varied significantly according to the stages of pregnancy (p < 0.05). At the genus level, the abundance of Treponema in pregnant donkeys was greater than that in non-pregnant donkeys (p < 0.05), and the genus Streptococcus reached its maximum abundance in the P2 period (p < 0.05). The abundance of Ruminococcaceae_NK4A214_group and norank_f_norank_o_WCHB1-41 linearly increased with the progression of pregnancy (p < 0.05). In addition, the host plasma metabolome was altered significantly during the gestation period. Testolic acid, estradiol-17beta 3-sulfate, equol 7’-o-glucuronide, equol 4’-o-glucuronide, estrone, estrone 3-glucuronide, and estradiol were the most significant differential enriched metabolites, and they increased gradually as gestation progressed. The altered metabolites were mainly enriched in pathways matched to bile secretion, ABC transporters, amino acid metabolism, protein digestion and absorption, mineral absorption, fatty acid degradation, glycerophospholipid metabolism, and steroid hormone biosynthesis. We also found a significant correlation between the shifts in donkey fecal bacteria and changes in the host metabolism. In summary, this study provided systematic data on the fecal bacterial changes and host plasma metabolism of donkeys throughout pregnancy. The results indicated that host–bacteria interactions during the gestation period influence the host metabolism. These interactions benefit the pregnant donkeys by providing a sufficient supply of nutrients and energy for fetal growth and maternal health.
Virus-to-prokaryote ratio in the Salar de Huasco and different ecosystems of the Southern hemisphere and its relationship with physicochemical and biological parameters
Authors: Eissler Yoanna , Castillo-Reyes Alonso , Dorador Cristina , Cornejo-D'Ottone Marcela , Celis-Plá Paula S. M. , Aguilar Polette , Molina Verónica
Published: August 2022

The virus-to-prokaryote ratio (VPR) has been used in many ecosystems to study the relationship between viruses and their hosts. While high VPR values indicate a high rate of prokaryotes' cell lysis, low values are interpreted as a decrease in or absence of viral activity. Salar de Huasco is a high-altitude wetland characterized by a rich microbial diversity associated with aquatic sites like springs, ponds, streams and a lagoon with variable physicochemical conditions. Samples from two ponds, Poza Rosada (PR) and Poza Verde (PV), were analyzed by epifluorescence microscopy to determine variability of viral and prokaryotic abundance and to calculate the VPR in a dry season. In addition, to put Salar de Huasco results into perspective, a compilation of research articles on viral and prokaryotic abundance, VPR, and metadata from various Southern hemisphere ecosystems was revised. The ecosystems were grouped into six categories: high-altitude wetlands, Pacific, Atlantic, Indian, and Southern Oceans and Antarctic lakes. Salar de Huasco ponds recorded similar VPR values (an average of 7.4 and 1.7 at PR and PV, respectively), ranging from 3.22 to 15.99 in PR. The VPR variability was associated with VA and chlorophyll a, when considering all data available for this ecosystem. In general, high-altitude wetlands recorded the highest VPR average (53.22 ± 95.09), followed by the Oceans, Southern (21.91 ± 25.72), Atlantic (19.57 ± 15.77) and Indian (13.43 ± 16.12), then Antarctic lakes (11.37 ± 15.82) and the Pacific Ocean (6.34 ± 3.79). Physicochemical variables, i.e., temperature, conductivity, nutrients (nitrate, ammonium, and phosphate) and chlorophyll a as a biological variable, were found to drive the VPR in the ecosystems analyzed. Thus, the viral activity in the Wetland followed similar trends of previous reports based on larger sets of metadata analyses. In total, this study highlights the importance of including viruses as a biological variable to study microbial temporal dynamics in wetlands considering their crucial role in the carbon budgets of these understudied ecosystems in the southern hemisphere.
The role and mechanisms of gut microbiota in diabetic nephropathy, diabetic retinopathy and cardiovascular diseases
Authors: Lv Qiulan , Li Zhiyuan , Sui Aihua , Yang Xiaomin , Han Yafei , Yao Ruyong
Published: August 2022

Type 2 diabetes mellitus (T2DM) and T2DM-related complications [such as retinopathy, nephropathy, and cardiovascular diseases (CVDs)] are the most prevalent metabolic diseases. Intriguingly, overwhelming findings have shown a strong association of the gut microbiome with the etiology of these diseases, including the role of aberrant gut bacterial metabolites, increased intestinal permeability, and pathogenic immune function affecting host metabolism. Thus, deciphering the specific microbiota, metabolites, and the related mechanisms to T2DM-related complications by combined analyses of metagenomics and metabolomics data can lead to an innovative strategy for the treatment of these diseases. Accordingly, this review highlights the advanced knowledge about the characteristics of the gut microbiota in T2DM-related complications and how it can be associated with the pathogenesis of these diseases. Also, recent studies providing a new perspective on microbiota-targeted therapies are included.
Gut microbiota supports male reproduction via nutrition, immunity, and signaling
Authors: Cai Hui , Cao Xuanhong , Qin Dezhe , Liu Yundie , Liu Yang , Hua Jinlian , Peng Sha
Published: August 2022

Gut microbiota (GM) is a major component of the gastrointestinal tract. Growing evidence suggests that it has various effects on many distal organs including the male reproductive system in mammals. GM and testis form the gut-testis axis involving the production of key molecules through microbial metabolism or de novo synthesis. These molecules have nutrition, immunity, and hormone-related functions and promote the male reproductive system via the circulatory system. GM helps maintain the integral structure of testes and regulates testicular immunity to protect the spermatogenic environment. Factors damaging GM negatively impact male reproductive function, however, the related mechanism is unknown. Also, the correlation between GM and testis remains to be yet investigated. This review discusses the complex influence of GM on the male reproductive system highlighting the impact on male fertility.
The multi-domain exercise intervention for memory and brain function in late middle-aged and older adults at risk for Alzheimer's disease: A protocol for Western–Eastern Brain Fitness Integration Training trial
Authors: Chang Yu-Kai , Erickson Kirk I. , Aghjayan Sarah L. , Chen Feng-Tzu , Li Ruei-Hong , Shih Jia-Ru , Chang Shao-Hsi , Huang Chih-Mao , Chu Chien-Heng
Published: August 2022

Background

Aging is associated with cognitive decline, increased risk for dementia, and deterioration of brain function. Modifiable lifestyle factors (e.g., exercise, meditation, and social interaction) have been proposed to benefit memory and brain function. However, previous studies have focused on a single exercise modality or a single lifestyle factor. Consequently, the effect of a more comprehensive exercise program that combines multiple exercise modalities and lifestyle factors, as well as examines potential mediators and moderators, on cognitive function and brain health in late middle-aged and older adults remains understudied. This study's primary aim is to examine the effect of a multi-domain exercise intervention on memory and brain function in cognitively healthy late middle-aged and older adults. In addition, we will examine whether apolipoprotein E (ApoE) genotypes, physical fitness (i.e., cardiovascular fitness, body composition, muscular fitness, flexibility, balance, and power), and brain-derived neurotrophic factor (BDNF) moderate and mediate the exercise intervention effects on memory and brain function.

Methods

The Western-Eastern Brain Fitness Integration Training (WE-BFit) is a single-blinded, double-arm, 6-month randomized controlled trial. One hundred cognitively healthy adults, aged 45–70 years, with different risks for Alzheimer's disease (i.e., ApoE genotype) will be recruited and randomized into either a multi-domain exercise group or an online educational course control group. The exercise intervention consists of one 90-min on-site and several online sessions up to 60 min per week for 6 months. Working memory, episodic memory, physical fitness, and BDNF will be assessed before and after the 6-month intervention. The effects of the WE-BFit on memory and brain function will be described and analyzed. We will further examine how ApoE genotype and changes in physical fitness and BDNF affect the effects of the intervention.

Discussion

WE-BFit is designed to improve memory and brain function using a multi-domain exercise intervention. The results will provide insight into the implementation of an exercise intervention with multiple domains to preserve memory and brain function in adults with genetic risk levels for Alzheimer's disease.

Clinical trial registration

ClinicalTrials.gov, identifier: NCT05068271.
Efficacy of acupuncture in animal models of vascular dementia: A systematic review and network meta-analysis
Authors: Li Guangyao , Shi Yuling , Zhang Lu , Yang Chuanghui , Wan Ting , Lv Hang , Jian Wenxuan , Li Jinghu , Li Min
Published: August 2022

Background and purpose

Acupuncture is widely used in clinical practice for the treatment of vascular diseases. However, the protocol, efficacy, and mechanism of acupuncture in animal models of vascular dementia are still controversial. Based on the above problems, we initiated this comprehensive study.

Methods

To analyze the literatures included in this study, 4 databases were searched and the SYRCLE's Risk of bias tool was employed. To perform the subgroup analysis of different acupuncture methods and the Review Manager 5.3 was applied. Meanwhile, the pairwise and network meta-analysis were conducted using Addis 1.16.8. The outcomes included escape latency, number of crossings, time spent in the target quadrant, and swimming speed.

Results

Forty-two studies with a total of 1,486 animals were included in this meta-analysis. According to the results from subgroup analysis, GV20 + ST36 (Baihui + bilateral Zusanli) combined with 14-day manual acupuncture can obtain best improvement of the rats cognitive function among all acupuncture regimens (MD: −23.41; 95%CI: −26.66, −20.15; I2 = 0%; P < 0.001). The heterogeneity of other acupuncture treatments was significantly higher than that of GV20 + ST36, because the treatment courses were not uniform. Pair-wise and network comparisons are highly consistent. The major results of the network meta-analysis were as follows, In comparison to the impaired group, the acupuncture group showed significantly reduced escape latency (MD: −25.87; 95%CI: −30.75, −21.12), increased number of original platform crossings (MD: 2.63; 95%CI: 1.94, 3.34) and time spent in the target quadrant (MD: 7.88; 95%CI: 4.25, 11.44). The overall results of the network meta-analysis are as follows: the normal and sham-operated groups performed the best, followed by medicine and acupuncture, while no effect was found in the impaired group treated with non-acupoint and palliative.

Conclusions

Acupuncture significantly improves cognitive function in rats with vascular dementia. Compared to other acupuncture plans, (GV20 + ST36, MA) and 14 -day manual acupuncture can be used to obtain better results. The main mechanism of acupuncture in the treatment of vascular dementia is reduced oxidative stress, neuronal inflammation, and apoptosis, as well as the increased synaptic plasticity and neurotransmitters.

Systematic review registration

https://inplasy.com/inplasy-2021-11-0036/, identifier: INPLASY2021110036.
Freezing of gait in Parkinson’s disease is associated with the microstructural and functional changes of globus pallidus internus
Authors: Kou Wenyi , Wang Xuemei , Zheng Yuanchu , Zhao Jiajia , Cai Huihui , Chen Huimin , Sui Binbin , Feng Tao
Published: August 2022

Background

Freezing of gait (FOG) is a common motor symptom in advanced Parkinson’s disease (PD). However, the pathophysiology mechanism of FOG is not fully understood. The purpose of this study was to investigate microstructural abnormalities in subcortical gray matter and alterations in functional connectivity of the nuclei with microstructural changes. In addition, the correlations between these microstructural and functional changes and the severity of FOG were measured.

Materials and methods

Twenty-four patients with FOG (PD-FOG), 22 PD patients without FOG (PD-nFOG), and 27 healthy controls (HC) were recruited. FOG Questionnaire (FOGQ) and Gait and Falling Questionnaire (GFQ) were assessed, and Timed Up and Go (TUG) tests were performed in PD-FOG patients. All subjects underwent diffusion tensor imaging (DTI) and resting-state functional MRI scanning. The DTI measures, including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), were extracted and measured from basal ganglia, thalamus, and substantia nigra. The nuclei with microstructural alterations were selected as seed regions to perform the seed-based resting-state functional connectivity.

Results

The MD and RD values of the right globus pallidus internus (GPi) were significantly higher in patients with PD-FOG compared with PD-nFOG patients and HC. In PD-FOG patients, the MD and RD values of the right GPi were significantly correlated with the time of the TUG test in both ON and OFF states. The MD values were also correlated with the GFQ scores in PD-FOG patients. Resting-state functional connectivity between the right GPi and left middle occipital gyri decreased significantly in PD-FOG patients compared to PD-nFOG patients, and was negatively correlated with GFQ scores as well as the time of ON state TUG in PD-FOG patients.

Conclusion

Microstructural alterations in the right GPi and functional connectivity between the right GPi and visual cortex may be associated with the pathophysiological mechanisms of FOG in PD patients.
Bimanual motor skill learning after stroke: Combining robotics and anodal tDCS over the undamaged hemisphere: An exploratory study
Authors: De Laet Chloë , Herman Benoît , Riga Audrey , Bihin Benoît , Regnier Maxime , Leeuwerck Maria , Raymackers Jean-Marc , Vandermeeren Yves
Published: August 2022

Background

Since a stroke can impair bimanual activities, enhancing bimanual cooperation through motor skill learning may improve neurorehabilitation. Therefore, robotics and neuromodulation with transcranial direct current stimulation (tDCS) are promising approaches. To date, tDCS has failed to enhance bimanual motor control after stroke possibly because it was not integrating the hypothesis that the undamaged hemisphere becomes the major poststroke hub for bimanual control.

Objective

We tested the following hypotheses: (I) In patients with chronic hemiparetic stroke training on a robotic device, anodal tDCS applied over the primary motor cortex of the undamaged hemisphere enhances bimanual motor skill learning compared to sham tDCS. (II) The severity of impairment correlates with the effect of tDCS on bimanual motor skill learning. (III) Bimanual motor skill learning is less efficient in patients than in healthy individuals (HI).

Methods

A total of 17 patients with chronic hemiparetic stroke and 7 healthy individuals learned a complex bimanual cooperation skill on the REAplan® neurorehabilitation robot. The bimanual speed/accuracy trade-off (biSAT), bimanual coordination (biCo), and bimanual force (biFOP) scores were computed for each performance. In patients, real/sham tDCS was applied in a crossover, randomized, double-blind approach.

Results

Compared to sham, real tDCS did not enhance bimanual motor skill learning, retention, or generalization in patients, and no correlation with impairment was noted. The healthy individuals performed better than patients on bimanual motor skill learning, but generalization was similar in both groups.

Conclusion

A short motor skill learning session with a robotic device resulted in the retention and generalization of a complex skill involving bimanual cooperation. The tDCS strategy that would best enhance bimanual motor skill learning after stroke remains unknown.

Clinical trial registration

https://clinicaltrials.gov/ct2/show/NCT02308852, identifier: NCT02308852.
A structural MRI study of global developmental delay in infants (<2 years old)
Authors: Sun Hui-miao , Li Qian-yun , Xiao Ru-yi , Zhang Ze-dong , Yang Xiao-yan , Yang Jie , Jin Bo , Wen Jia-xiang , Wu Yan-jun , Yang Hong , Wang Fan
Published: August 2022

Objective

To use structural magnetic resonance imaging (3D-MRI) to evaluate the abnormal development of the cerebral cortex in infants with global developmental delay (GDD).

Methods

The GDD group includes 67 infants aged between 112 and 699 days with global developmental delay and who underwent T1-weighted MRI scans in Shanxi Children's Hospital from December 2019 to March 2022. The healthy control (HC) group includes 135 normal developing infants aged between 88 and 725 days in Shanxi Children's Hospital from September 2020 to August 2021. Whole-brain T1-weighted MRI scans were carried out with a 3.0-T magnetic resonance scanner, which was later processed using InfantSurfer to perform MR image processing and cortical surface reconstruction. Two morphological features of the cortical surface of the 68 brain regions were computed, i.e., the cortical thickness (CT) and cortical surface area (SA), and compared between the GDD and HC groups.

Results

With regard to the CT, the HC group showed a rapid decrease at first and then a slow increase after birth, and the CT of the GDD group decreased slowly and then became relatively stable. The GDD group showed bilaterally higher hemispherical average CT than those in the HC group. In detail, for the left hemisphere, except in the entorhinal and temporal poles in which the average CT values of the two brain regions were lower than those of the HC group, the CT of the 26 brain regions in the GDD group was higher than those of the HC group (p < 0.05). For the right hemisphere, the CT of the entorhinal in the GDD group was lower than that in the HC group. Otherwise, the CT of the remaining 28 brain regions was higher than those in the HC group (p < 0.05). With regard to the SA, both groups showed a rapid increase after birth till 23 months and remained quite stable afterward. The GDD group shows lower SA bilaterally than that in the HC group. In detail, SA in the GDD group was lower in most cortical regions of both hemispheres than in the HC group (p < 0.05), except for the right temporal pole and entorhinal. When testing for brain asymmetry, we found that the HC group showed obvious asymmetry of CT and SA, while only a few cortical regions in the GDD group showed asymmetry.
Time-frequency signatures evoked by single-pulse deep brain stimulation to the subcallosal cingulate
Authors: Smith Ezra E. , Choi Ki Sueng , Veerakumar Ashan , Obatusin Mosadoluwa , Howell Bryan , Smith Andrew H. , Tiruvadi Vineet , Crowell Andrea L. , Riva-Posse Patricio , Alagapan Sankaraleengam , Rozell Christopher J. , Mayberg Helen S. , Waters Allison C.
Published: August 2022

Precision targeting of specific white matter bundles that traverse the subcallosal cingulate (SCC) has been linked to efficacy of deep brain stimulation (DBS) for treatment resistant depression (TRD). Methods to confirm optimal target engagement in this heterogenous region are now critical to establish an objective treatment protocol. As yet unexamined are the time-frequency features of the SCC evoked potential (SCC-EP), including spectral power and phase-clustering. We examined these spectral features—evoked power and phase clustering—in a sample of TRD patients (n = 8) with implanted SCC stimulators. Electroencephalogram (EEG) was recorded during wakeful rest. Location of electrical stimulation in the SCC target region was the experimental manipulation. EEG was analyzed at the surface level with an average reference for a cluster of frontal sensors and at a time window identified by prior study (50–150 ms). Morlet wavelets generated indices of evoked power and inter-trial phase clustering. Enhanced phase clustering at theta frequency (4–7 Hz) was observed in every subject and was significantly correlated with SCC-EP magnitude, but only during left SCC stimulation. Stimulation to dorsal SCC evinced stronger phase clustering than ventral SCC. There was a weak correlation between phase clustering and white matter density. An increase in evoked delta power (2–4 Hz) was also coincident with SCC-EP, but was less consistent across participants. DBS evoked time-frequency features index mm-scale changes to the location of stimulation in the SCC target region and correlate with structural characteristics implicated in treatment optimization. Results also imply a shared generative mechanism (inter-trial phase clustering) between evoked potentials evinced by electrical stimulation and evoked potentials evinced by auditory/visual stimuli and behavioral tasks. Understanding how current injection impacts downstream cortical activity is essential to building new technologies that adapt treatment parameters to individual differences in neurophysiology.
A comparison of placebo and nocebo effects on objective and subjective postural stability: a double-edged sword?
Authors: Russell Katherine , Duncan Michael , Price Michael , Mosewich Amber , Ellmers Toby , Hill Mathew
Published: August 2022

Background: Positive expectations (i.e., placebo effect) can improve postural control during quiet standing. This raises an important question: if postural control is susceptible to positive expectations, is it possible to elicit the opposite, a decline in postural stability, simply by suggesting a performance impairment (i.e., nocebo) will take place? Yet no studies have examined the nocebo effect on balance performance. To better understand both phenomena, comparative studies, which include both placebo and nocebo conditions, are needed.

Method: Forty-two healthy adults were initially assessed for objective (center of pressure movement) and subjective (perceived) postural stability and performance expectations. Participants were then randomly assigned in equal numbers to a placebo (positive expectation), nocebo (negative expectation) or control (no suggestion) group. Participants in the placebo/nocebo groups were deceptively administered an inert capsule described as a potent supplement which would either positively or negatively influence their balance performance. Objective and subjective postural stability, and performance expectations were reassessed 20 min later.

Results: The nocebo procedure evoked an increase in COP sway movements and reduced perceived stability compared to a control group. The placebo group presented with reductions COP sway movements and increased perceived stability following expectation manipulation. Compared to the control group, the placebo group showed a significantly higher performance expectation whilst the nocebo group showed a significantly lower performance expectation. Regression analyses also revealed that performance expectations following the placebo/nocebo procedure significantly predicted perceptions of postural instability (i.e., perceived performance), accounting for around 50% of the variance. These results remained even when controlling for actual performance (i.e., objective postural stability).

Conclusion: Our findings indicate that positive and negative performance expectations evoked by instructional manipulation can profoundly influence both objective and subjective postural stability. Postural control—and perceptions regarding such—are clearly susceptible to expectation manipulation, which could have important practical implications and repercussions on testing, training interventions and rehabilitation programs. Positive and negative expectancies are a double-edged sword for postural control.