bluuebunny/crossref_metadata_2025 huggingface dataset:
PD-1 inhibitors plus oxaliplatin or cisplatin-based chemotherapy in first-line treatments for advanced gastric cancer: A network meta-analysis
Authors: Guo Xiaoyu , Yang Bowen , He Lingzi , Sun Yiting , Song Yujia , Qu Xiujuan
Published: August 2022

Background

Currently, there has been no direct comparison between programmed cell death protein 1 (PD-1) inhibitors plus different chemotherapy regimens in first-line treatments for advanced gastric cancer (AGC). This study performed a network meta-analysis (NMA) to evaluate the efficacy and safety of PD-1 inhibitors plus oxaliplatin- or cisplatin-based chemotherapy.

Methods

PubMed, Embase, and the Cochrane Central Register were used to seek a series of phase III randomized controlled trials (RCTs) studying on first-line PD-1 inhibitors plus chemotherapy and phase III RCTs comparing first-line oxaliplatin and cisplatin-based chemotherapy for AGC to perform NMA. The main outcome was overall survival (OS) and other outcomes included progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAEs).

Results

Eight eligible RCTs involving 5723 patients were included. Compared with PD-1 inhibitors plus cisplatin-based chemotherapy, PD-1 inhibitors plus oxaliplatin-based chemotherapy could prolong the OS without statistical significance (hazard ratio [HR]: 0.82, 95% credible interval [CI]: 0.63-1.06). However, for patients with combined positive score (CPS) ≥ 1, PD-1 inhibitors plus oxaliplatin-based chemotherapy significantly prolonged the OS (HR: 0.75, 95% CI: 0.57-0.99). PFS in PD-1 inhibitors plus oxaliplatin-based chemotherapy was significantly longer than that in PD-1 inhibitors plus cisplatin-based chemotherapy (HR: 0.72, 95% CI: 0.53-0.99). Regarding safety, the incidence of ≥ 3 TRAEs was similar between PD-1 inhibitors plus oxaliplatin-based chemotherapy and PD-1 inhibitors plus cisplatin-based chemotherapy (RR: 0.86, 95% CI: 0.66-1.12). The surface under the cumulative ranking area curve (SUCRA) indicated that PD-1 inhibitors plus oxaliplatin-based chemotherapy ranked first for OS (97.7%), PFS (99.3%), and ORR (89.0%). For oxaliplatin-based regimens, there was no significant difference between nivolumab plus oxaliplatin-based chemotherapy and sintilimab plus oxaliplatin-based chemotherapy in terms of OS, PFS, ORR, and ≥3 TRAEs.

Conclusion

Compared with PD-1 inhibitors plus cisplatin-based chemotherapy, PD-1 inhibitors plus oxaliplatin-based chemotherapy significantly prolonged PFS. Considering both efficacy and safety, PD-1 inhibitors plus oxaliplatin-based chemotherapy might be a better option in the first-line treatment for AGC.
Metabolic rewiring directs melanoma immunology
Authors: Sun Ningyue , Tian Yangzi , Chen Yuhan , Guo Weinan , Li Chunying
Published: August 2022

Melanoma results from the malignant transformation of melanocytes and accounts for the most lethal type of skin cancers. In the pathogenesis of melanoma, disordered metabolism is a hallmark characteristic with multiple metabolic paradigms involved in, e.g., glycolysis, lipid metabolism, amino acid metabolism, oxidative phosphorylation, and autophagy. Under the driving forces of oncogenic mutations, melanoma metabolism is rewired to provide not only building bricks for macromolecule synthesis and sufficient energy for rapid proliferation and metastasis but also various metabolic intermediates for signal pathway transduction. Of note, metabolic alterations in tumor orchestrate tumor immunology by affecting the functions of surrounding immune cells, thereby interfering with their antitumor capacity, in addition to the direct influence on tumor cell intrinsic biological activities. In this review, we first introduced the epidemiology, clinical characteristics, and treatment proceedings of melanoma. Then, the components of the tumor microenvironment, especially different populations of immune cells and their roles in antitumor immunity, were reviewed. Sequentially, how metabolic rewiring contributes to tumor cell malignant behaviors in melanoma pathogenesis was discussed. Following this, the proceedings of metabolism- and metabolic intermediate-regulated tumor immunology were comprehensively dissertated. Finally, we summarized currently available drugs that can be employed to target metabolism to intervene tumor immunology and modulate immunotherapy.
Post-translational changes in Phialophora verrucosa via lysine lactylation during prolonged presence in a patient with a CARD9-related immune disorder
Authors: Song Yinggai , Liu Xiao , Stielow J. Benjamin , de Hoog Sybren , Li Ruoyu
Published: August 2022

CARD9-related inherited immune disorders are a major risk factor for chronic disseminated fungal infection. In addition to pathogens of Candida and dermatophytes, the environmental opportunists of the black yeast-like fungi are relatively frequent in this patient cohort. Particularly the genus Phialophora is overrepresented. We investigated two isolates of a strain of P. verrucosa residing in a CARD9 patient, sampled with a period of ten years apart. Genomes, melanization and antifungal susceptibility of progenitor and derived strains were compared, and potential adaptation to the host habitat was investigated with proteomic techniques using post-translational modification as a proxy. Global lactylation analysis was performed using high accuracy nano-LC-MS/MS in combination with enrichment of lactylated peptides from digested cell lysates, and subsequent peptide identification. The genome of the derived isolate had accumulated 6945 SNPs, of which 31 were detected in CDS. A large number of identified proteins were significantly enriched, e.g. in melanin biosynthesis. A total of 636 lactylation sites on 420 lactylated proteins were identified, which contained in 26 types of modification motifs. Lysine lactylation (Kla) was found in 23 constituent proteins of the ribosome, indicating an impact of Kla in protein synthesis. Twelve lactylated proteins participated in pathogenicity. A protein-protein interaction (PPI) network analysis suggested that protein lactylations are widely distributed influencing various biological processes. Our findings reveal widespread roles for lysine lactylation in regulating metabolism and melanin biosynthesis in black fungi. Several large rearrangements and inversions were observed in the genome, but genomic changes could not be linked to adaptation or to known clinically relevant properties of progenitor to derived isolate; in vitro antifungal susceptibility had largely remained unaltered.
Growth as a function of sea ice cover, light and temperature in the arctic/subarctic coralline C. compactum: A year-long in situ experiment in the high arctic
Authors: Gould Jessica , Halfar Jochen , Adey Walter , Ries Justin B.
Published: August 2022

Long-term, high-resolution measurements of environmental variability are sparse in the High Arctic. In the absence of such data, we turn to proxies recorded in the layered skeletons of the long-lived crustose coralline algae Clathromorphum compactum. Annual growth banding in this alga is dependent on several factors that include temperature, light availability, nutrients, salinity, and calcium carbonate saturation state. It has been observed that growth slows during winter as sunlight reaching the seafloor diminishes due to decreased insolation and the build-up of sea-ice, such that the relationship between sea-ice cover extent and algal growth has allowed for reconstructions of relative sea-ice variability through time. However, recent laboratory work has shown that C. compactum continue growing in complete darkness (sea-ice cover). Therefore, a more complete understanding of algal growth is necessary for the refinement of the sea-ice proxy. Here, we present the results of a ~year-long in-situ growth and environmental monitoring experiment in Arctic Bay, Nunavut, Canada (~73°N) which addresses, for the first time in situ, the gaps in our understanding of growth over an annual cycle in the High Arctic. Algal growth was assessed on a quasi-monthly basis, where specimens were subsampled to quantify monthly extension in the context of ocean temperature and light availability. By measuring extension rate through time, we observed that the algae grew on average 72 µm yr-1, with ~54% of annual growth occurring during the sea-ice free summer months (June-September), ~25% during the winter months (November-April), and ~21% occurring during the transition months of May and October. Although winter growth slowed, we did not observe a consistent cessation of linear extension during low-or no-light months. We posit that substantial growth during the winter months at this latitude is most likely a consequence of the mobilization of stored energy (photosynthate) produced during the photosynthetically active summer months. However, we also discuss the possibility of low light-photosynthetic activity and/or dark carbon fixation, which could also facilitate extension through time. Overall, the novel growth model presented here has implications for the use of C. compactum growth for reconstructing the environment as well as for trace-element-based (typically Mg/Ca) algal chronologies.
Genome-wide characterization of laccase gene family in Schizophyllum commune 20R-7-F01, isolated from deep sediment 2 km below the seafloor
Authors: Liu Xuan , Zain ul Arifeen Muhammad , Xue Yarong , Liu Changhong
Published: August 2022

Laccases are ligninolytic enzymes that play a crucial role in various biological processes of filamentous fungi, including fruiting-body formation and lignin degradation. Lignin degradation is a complex process and its degradation inSchizophyllum communeis greatly affected by the availability of oxygen. Here, a total of six putative laccase genes (ScLAC) were identified from theS. commune20R-7-F01 genome. These genes, which include three typical Cu-oxidase domains, can be classified into three groups based on phylogenetic analysis.ScLACshowed distinct intron-exon structures and conserved motifs, suggesting the conservation and diversity ofScLACin gene structures. Additionally, the number and type of cis-acting elements, such as substrate utilization-, stress-, cell division- and transcription activation-related cis-elements, varied betweenScLACgenes, suggesting that the transcription of laccase genes inS. commune20R-7-F01 could be induced by different substrates, stresses, or other factors. The SNP analysis of resequencing data demonstrated that theScLACofS. communeinhabiting deep subseafloor sediments were significantly different from those ofS. communeinhabiting terrestrial environments. Similarly, the large variation of conserved motifs number and arrangement of laccase between subseafloor and terrestrial strains indicated thatScLAChad a diverse structure. The expression ofScLAC5andScLAC6genes was significantly up-regulated in lignin/lignite medium, suggesting that these two laccase genes might be involved in fungal utilization and degradation of lignite and lignin under anaerobic conditions. These findings might help in understanding the function of laccase in white-rot fungi and could provide a scientific basis for further exploring the relationship between the LAC family and anaerobic degradation of lignin byS. commune.
Cangma Huadu granules attenuate H1N1 virus-induced severe lung injury correlated with repressed apoptosis and altered gut microbiome
Authors: Liu Mingjiang , Liu Tengwen , Wang Xuerui , Yu Chenglong , Qin Tao , Li Jingui , Zhang Mina , Li Zhenxuan , Cui Xuran , Xu Xiaolong , Liu Qingquan
Published: August 2022

Severe influenza A virus infection leads to overwhelming inflammatory responses and cellular apoptosis, which causes lung injury and contributes to high mortality and morbidity. The gut microbiome altered in response to the infection might influence the disease progression and the treatment outcome. Cangma Huadu (CMHD) granules, an in-hospital preparation of traditional Chinese medicine, have been shown to be favorable in the clinical treatment of influenza. However, the effects and mechanisms of CMHD granules on severe influenza pneumonia and its mechanisms are not well-known. In this study, a lethal influenza A (H1N1) A/Puerto Rico/8/34 virus (PR8)-infected mice model was established, and the 16S ribosomal RNA (16S rRNA) V3–V4 region sequencing of the intestinal microbiome was conducted. We revealed that the oral administration of CMHD granules protects mice against higher mortality, enhanced weight loss, overwhelmed interferon-γ concentration, lung viral titers, and severe lung pathological injury in PR8-infected mice. CMHD granules’ administration downregulated the levels of interleukin (IL)-1β, tumor necrosis factor-α, and malondialdehyde, while it upregulated the levels of IL-10, superoxide dismutase, and glutathione peroxidase. Subsequently, it decreased the protein ratio of B-cell lymphoma-2/Bcl-2-associated X and the expression of cleaved caspase-3. The diversity and compositions of the gut microbes were altered profoundly after the administration of CMHD granules in PR8-infected mice. A higher abundance of Bifidobacterium, Parasutterella, Bacteroides, and Faecalibaculum was observed in the CMHD group, and a higher abundance of Lactobacillus and Turicibacter was observed in the positive drug Ribavirin group. The linear discriminant analysis effect size also revealed a higher proportion of Bacteroides and Bifidobacterium_pseudolongum characterized in the CMHD group. These results demonstrated that CMHD granules are a promising strategy for managing severe influenza and attenuating severe lung damage via reducing viral titer, inflammatory responses, and oxidative stress. The mechanisms are involved in repressed Bcl-2-regulated apoptosis and altered composition and diversity of the gut microbiome.
Spatial patterns of benthic biofilm diversity among streams draining proglacial floodplains
Authors: Brandani Jade , Peter Hannes , Busi Susheel Bhanu , Kohler Tyler J. , Fodelianakis Stilianos , Ezzat Leila , Michoud Grégoire , Bourquin Massimo , Pramateftaki Paraskevi , Roncoroni Matteo , Lane Stuart N. , Battin Tom J.
Published: August 2022

Glacier shrinkage opens new proglacial terrain with pronounced environmental gradients along longitudinal and lateral chronosequences. Despite the environmental harshness of the streams that drain glacier forelands, their benthic biofilms can harbor astonishing biodiversity spanning all domains of life. Here, we studied the spatial dynamics of prokaryotic and eukaryotic photoautotroph diversity within braided glacier-fed streams and tributaries draining lateral terraces predominantly fed by groundwater and snowmelt across three proglacial floodplains in the Swiss Alps. Along the lateral chronosequence, we found that benthic biofilms in tributaries develop higher biomass than those in glacier-fed streams, and that their respective diversity and community composition differed markedly. We also found spatial turnover of bacterial communities in the glacier-fed streams along the longitudinal chronosequence. These patterns along the two chronosequences seem unexpected given the close spatial proximity and connectivity of the various streams, suggesting environmental filtering as an underlying mechanism. Furthermore, our results suggest that photoautotrophic communities shape bacterial communities across the various streams, which is understandable given that algae are the major source of organic matter in proglacial streams. Overall, our findings shed new light on benthic biofilms in proglacial streams now changing at rapid pace owing to climate-induced glacier shrinkage.
Soil microbial communities response to different fertilization regimes in young Catalpa bungei plantation
Authors: Guan Zhuizhui , Lin Daiyi , Chen Dong , Guo Yundan , Lu Yizeng , Han Qingjun , Li Ningning , Su Yan , Li Jiyue , Wang Junhui , Ma Wenjun , Qiu Quan , He Qian
Published: August 2022

Fertilization is a fundamental aspect of global forest management that enhances forest productivity and drastically affects soil microbial communities. However, few studies have investigated the differences and similarities in the responses of below-ground microbial communities to different fertilization schemes. The effects of fertilization regimes on the composition and diversity of soil fungal and bacterial communities were investigated in a young Catalpa bungei plantation in Shandong Province, Eastern China. Soil microbial communities were assessed undergoing three types of fertilization: (i) no fertilization (CK), (ii) hole fertilization (HF), and (iii) the integration of water and fertilizer (WF). We further analyzed the effects of soil depth (i.e., 0–20 and 20–40 cm) on the structure of soil microbial communities. Our results indicated that the diversity of bacteria (e.g., Chao1 and Shannon indices) reduced undergoing fertilization, and WF had a higher negative impact on bacterial diversity than HF. A lower bacterial diversity was observed in the subsoil compared to the topsoil. In contrast to bacterial diversity, fungal diversity had a slightly increasing trend in the fertilized environments. The primary bacterial function was metabolism, which was independent of fertilization or soil depth. Among fungal functional guilds, symbiotic soil fungi decreased obviously in the fertilized stand, whereas saprotrophic fungi increased slowly. According to the structural equation models (SEM), the diversity and composition of bacterial and fungal communities were jointly regulated by soil nutrients (including N and P contents) directly affected by fertilization and soil layer. These findings could be used to develop management practices in temperate forests and help sustain soil microbial diversity to maintain long-term ecosystem function and services.
Mode of action of elasnin as biofilm formation eradicator of methicillin-resistant Staphylococcus aureus
Authors: Long Lexin , Sulaiman Jordy Evan , Xiao Yao , Cheng Aifang , Wang Ruojun , Malit Jessie James , Wong Wai Chuen , Liu Wenchao , Li Yong-Xin , Chen Feng , Lam Henry , Qian Pei-Yuan
Published: August 2022

Biofilm is made up of microbes and their extracellular matrix, making microorganisms highly tolerant, resistant, and resilient to a wide range of antimicrobials. Biofilm treatment with conventional antimicrobial agents can accelerate the evolution and spread of resistance due to the reduced efficacy and increased gene transfer and differentiation within biofilms. Therefore, effective biofilm-targeting compounds are currently highly sought after. In the present study, we identified elasnin as a potent biofilm-targeting compound against methicillin-resistant Staphylococcus aureus (MRSA). Elasnin effectively inhibited biofilm formation and especially eradicated the pre-formed biofilms of MRSA with low cytotoxicity and low risk of resistance development and retains its activity in a chronic wound biofilms model. A comprehensive mechanistic study using multi-omics and confocal and scanning electron microscopy revealed that elasnin induced the biofilm matrix destruction in a time-dependent manner and interfered with the cell division during the exponential phase, primarily by repressing the expression of virulence factors. Cells released from the elasnin-treated biofilms exhibited a defective appearance and became more sensitive to beta-lactam antibiotic penicillin G. Through gene overexpression and deletion assay, we discovered the key role of sarZ during elasnin-induced biofilm eradication. Overall, the present study identified elasnin as a potent biofilm eradicator against MRSA that harbors potential to be developed for biofilm removal and chronic wound treatment, and provided new insights into the molecular targets for biofilm eradication in MRSA.
Comparative evaluation of the microbial diversity and metabolite profiles of Japanese-style and Cantonese-style soy sauce fermentation
Authors: Tan Guiliang , Wang Yi , Hu Min , Li Xueyan , Li Xiangli , Pan Ziqiang , Li Mei , Li Lin , Zheng Ziyi
Published: August 2022

Microorganisms play essential roles in flavor formation during soy sauce fermentation. Different soy sauce fermentation types significantly affect flavor formation. However, comparisons of microbial communities and metabolites between different fermentation types have been little studied. Here, we investigated variation in microbial communities, metabolite profiles, and metabolic pathways during Japanese-type (JP) and Cantonese-type (CP) fermentation. Free amino acids and volatile compound profiles varied significantly between fermentation types, with JP samples containing higher contents of esters (39.84%; p < 0.05), alcohols (44.70%; p < 0.05) in the 120 d fermentation samples. Volatile compound profiles varied significantly between fermentation types, with JP samples containing higher contents of esters, alcohols, and free amino acids (p < 0.05). Metagenomic analysis indicated that both JP and CP communities were dominated by Tetragenococcus, Staphylococcus, Weissella (bacteria), and Aspergillus (fungi), but the two communities varied differently over time. Tetragenococcus drastically increased in abundance throughout the fermentation (from 0.02 to 59.2%) in JP fermentation, whereas Tetragenococcus (36.7%) and Staphylococcus (29.7%) dominated at 120 d of fermentation in CP fermentation. Metagenomic functional profiles revealed that the abundances of most genes involved with carbohydrate, amino acid, and lipid metabolism exhibited significant differences between fermentation types (p < 0.05) during the middle to late fermentation stages. Furthermore, predicted metabolic pathways for volatile substance biosynthesis differed between JP and CP fermentation, likely explaining the differences in flavor metabolite profiles. In addition, most of the genes associated with flavor generation were affiliated with Tetragenococcus, Weissella, Staphylococcus, Bacillus, and Aspergillus, suggesting that these microbes play important roles in flavor production during soy sauce fermentation. This study significantly improves our understanding of microbial functions and their metabolic roles in flavor formation during different soy sauce fermentation processes.
Predicting higher-order mutational effects in an RNA enzyme by machine learning of high-throughput experimental data
Authors: Beck James D. , Roberts Jessica M. , Kitzhaber Joey M. , Trapp Ashlyn , Serra Edoardo , Spezzano Francesca , Hayden Eric J.
Published: August 2022

Ribozymes are RNA molecules that catalyze biochemical reactions. Self-cleaving ribozymes are a common naturally occurring class of ribozymes that catalyze site-specific cleavage of their own phosphodiester backbone. In addition to their natural functions, self-cleaving ribozymes have been used to engineer control of gene expression because they can be designed to alter RNA processing and stability. However, the rational design of ribozyme activity remains challenging, and many ribozyme-based systems are engineered or improved by random mutagenesis and selection (in vitro evolution). Improving a ribozyme-based system often requires several mutations to achieve the desired function, but extensive pairwise and higher-order epistasis prevent a simple prediction of the effect of multiple mutations that is needed for rational design. Recently, high-throughput sequencing-based approaches have produced data sets on the effects of numerous mutations in different ribozymes (RNA fitness landscapes). Here we used such high-throughput experimental data from variants of the CPEB3 self-cleaving ribozyme to train a predictive model through machine learning approaches. We trained models using either a random forest or long short-term memory (LSTM) recurrent neural network approach. We found that models trained on a comprehensive set of pairwise mutant data could predict active sequences at higher mutational distances, but the correlation between predicted and experimentally observed self-cleavage activity decreased with increasing mutational distance. Adding sequences with increasingly higher numbers of mutations to the training data improved the correlation at increasing mutational distances. Systematically reducing the size of the training data set suggests that a wide distribution of ribozyme activity may be the key to accurate predictions. Because the model predictions are based only on sequence and activity data, the results demonstrate that this machine learning approach allows readily obtainable experimental data to be used for RNA design efforts even for RNA molecules with unknown structures. The accurate prediction of RNA functions will enable a more comprehensive understanding of RNA fitness landscapes for studying evolution and for guiding RNA-based engineering efforts.
Single-cell transcriptomics uncover the key ferroptosis regulators contribute to cancer progression in head and neck squamous cell carcinoma
Authors: Liu Fei , Tang Lindong , Li Qing , Chen Leihui , Pan Yuyue , Yin Zhao , He Jingjun , Tian Junzhang
Published: August 2022

The mechanism underlying the association between the development of head and neck squamous cell carcinoma (HNSCC) and ferroptosis is unclear. We analyzed the transcriptomes of 5902 single cells from a single-cell RNA-sequencing (scRNA-seq) dataset. They then aggregate into B cells, epithelial cells, fibroblasts, germ cells, mesenchymal cells, cancer stem cells, stem cells, T cells and endometrial cells, respectively. Our study shows that multiple pathways are significantly enriched in HNSCC development including extracellular matrix structural components, humoral immune responses, and muscle contraction. Differentially expressed genes analysis in Pseudotime analysis, pathway and biological function indicated that there was a significant correlation in the ferroptosis pathway. Furthermore, higher ferroptosis potential index (FPI) scores were significantly associated with worse overall survival prognosis in HNSCC patients. Pseudo-temporal, survival analyses and immunohistochemistry identified multiple central genes in HNSCC development, including ACSL1, SLC39A14, TFRC, and PRNP genes, and indicated associated ferroptosis. Overall, our study detected ferroptosis-related features is closely correlated with HNSCC prognosis and development, and deserved candidates suitable for immunotherapy treatment strategies determination for HNSCC patients.
Remote ischemic conditioning for acute ischemic stroke part 2: Study protocol for a randomized controlled trial
Authors: Ishizuka Kentaro , Hoshino Takao , Toi Sono , Mizuno Takafumi , Hosoya Megumi , Saito Moeko , Sato Yasuto , Yagita Yoshiki , Todo Kenichi , Sakaguchi Manabu , Ohashi Takashi , Maruyama Kenji , Hino Shuji , Honma Yutaka , Doijiri Ryosuke , Yamagami Hiroshi , Iguchi Yasuyuki , Hirano Teruyuki , Kimura Kazumi , Kitazono Takanari , Kitagawa Kazuo
Published: August 2022

Background

Remote ischemic conditioning (RIC) refers to the application of repeated short periods of ischemia intended to protect remote areas against tissue damage during and after prolonged ischemia.

Aim

We aim to evaluate the efficacy of RIC, determined by the modified Rankin Scale (mRS) score at 90 days after stroke onset.

Design and methods

This study is an investigator-initiated, multicenter, prospective, randomized, open-label, parallel-group clinical trial. The sample size is 400, comprising 200 patients who will receive RIC and 200 controls. The patients will be divided into three groups according to their National Institutes of Health Stroke Scale score at enrollment: 5–9, mild; 10–14, moderate; 15–20, severe. The RIC protocol will be comprised of four cycles, each consisting of 5 min of blood pressure cuff inflation (at 200 mmHg or 50 mmHg above the systolic blood pressure) followed by 5 min of reperfusion, with the cuff placed on the thigh on the unaffected side. The control group will only undergo blood pressure measurements before and after the intervention period. This trial is registered with the UMIN Clinical Trial Registry (https://www.umin.ac.jp/: UMIN000046225).

Study outcome

The primary outcome will be a good functional outcome as determined by the mRS score at 90 days after stroke onset, with a target mRS score of 0–1 in the mild group, 0–2 in the moderate group, and 0–3 in the severe group.

Discussion

This trial may help determine whether RIC should be recommended as a routine clinical strategy for patients with ischemic stroke.
Self-efficacy beliefs in managing positive emotions: Associations with positive affect, negative affect, and life satisfaction across gender and ages
Authors: Caprara Mariagiovanna , Gerbino Maria , Mebane Minou Ella , Ramirez-Uclés Isabel M.
Published: August 2022

Two studies were carried out on a Spanish population to explore the extent to which different self-efficacy beliefs in managing positive emotions are associated with common indicators of wellbeing, such as positive and negative affect or life satisfaction. The first study was conducted on 483 participants and attested to the factorial structure of three different self-efficacy beliefs: (a) perceived self-efficacy in expressing positive emotions; (b) perceived self-efficacy in retrieving memories of positive emotional experiences; and (c) perceived self-efficacy in using humor. The second study was carried out on 1,087 individuals between 19 and 80 years of age, and it provided evidence of the factorial invariance of the scales across age and gender. Furthermore, this latter study showed the association of self-efficacy in managing positive affect (SEMPA) with high chronic positive and low negative affect, and with high life satisfaction, controlling for gender and age. In younger participants, stronger associations were found between perceived self-efficacy in using humor and life satisfaction compared to older subjects. These findings may guide the design of interventions aimed at enhancing the potential benefits that could be drawn from the proper management of positive emotions.
Functional characterization of nutraceuticals using spectral clustering: Centrality of caveolae-mediated endocytosis for management of nitric oxide and vitamin D deficiencies and atherosclerosis
Authors: Fliri Anton Franz , Kajiji Shama
Published: August 2022

It is well recognized that redox imbalance, nitric oxide (NO), and vitamin D deficiencies increase risk of cardiovascular, metabolic, and infectious diseases. However, clinical studies assessing efficacy of NO and vitamin D supplementation have failed to produce unambiguous efficacy outcomes suggesting that the understanding of the pharmacologies involved is incomplete. This raises the need for using systems pharmacology tools to better understand cause-effect relationships at biological systems levels. We describe the use of spectral clustering methodology to analyze protein network interactions affected by a complex nutraceutical, Cardio Miracle (CM), that contains arginine, citrulline, vitamin D, and antioxidants. This examination revealed that interactions between protein networks affected by these substances modulate functions of a network of protein complexes regulating caveolae-mediated endocytosis (CME), TGF beta activity, vitamin D efficacy and host defense systems. Identification of this regulatory scheme and the working of embedded reciprocal feedback loops has significant implications for treatment of vitamin D deficiencies, atherosclerosis, metabolic and infectious diseases such as COVID-19.
Preparation of starch-based functional food nano-microcapsule delivery system and its controlled release characteristics
Authors: Tian Shuangqi , Xue Xing'ao , Wang Xinwei , Chen Zhicheng
Published: August 2022

Most of the functional substances in food are absorbed in the small intestine, but before entering the small intestine, the strong acid and enzymes in the stomach limit the amount that can reach the small intestine. Therefore, in this paper, to develop a delivery system for functional food ingredients, maintain the biological activity of the ingredients, and deliver them to the target digestive organs, preparation of starch-based functional food nano-microcapsule delivery system and its controlled release characteristics were reviewed. Embedding unstable food active ingredients in starch-based nano-microcapsules can give the core material excellent stability and certain functional effects. Starch-based wall materials refer to a type of natural polymer material that uses starch or its derivatives to coat fat-soluble components with its hydrophobic cavities. The preparation methods of starch-based wall materials mainly include spray drying, extrusion, freeze drying, ultra-high pressure, coagulation, fluidized bed coating, molecular inclusion, chemical, and enzymic methods. The controlled release of functional food can be achieved by preparing starch-based nano-microcapsules to encapsulate the active agents. It has been reported that that compared with traditional embedding agents such as gelatin, acacia gum, and xanthan gum, starch-based functional food nano-microcapsule delivery system had many good properties, including improving antioxidant capacity, bioavailability, probiotics, and concealing bad flavors. From this review, we can learn which method should be chosen to prepare starch-based functional food nano-microcapsule delivery system and understand the mechanism of controlled release.
Comparison of perioperative outcomes with or without routine chest tube drainage after video-assisted thoracoscopic pulmonary resection: A systematic review and meta-analysis
Authors: Li Rongyang , Qiu Jianhao , Qu Chenghao , Ma Zheng , Wang Kun , Zhang Yu , Yue Weiming , Tian Hui
Published: August 2022

Background

In recent years, an increasing number of thoracic surgeons have attempted to apply no routine chest tube drainage (NT) strategy after thoracoscopic lung resection. However, the safety and feasibility of not routinely placing a chest tube after lung resection remain controversial. This study aimed to investigate the effect of NT strategy after thoracoscopic pulmonary resection on perioperative outcomes.

Methods

A comprehensive literature search of PubMed, Embase, and the Cochrane Library databases until 3 January 2022 was performed to identify the studies that implemented NT strategy after thoracoscopic pulmonary resection. Perioperative outcomes were extracted by 2 reviewers independently and then synthesized using a random-effects model. Risk ratio (RR) and standardized mean difference (SMD) with 95% confidence interval (CI) served as the summary statistics for meta-analysis. Subgroup analysis and sensitivity analysis were subsequently performed.

Results

A total of 12 studies with 1,381 patients were included. The meta-analysis indicated that patients in the NT group had a significantly reduced postoperative length of stay (LOS) (SMD = -0.91; 95% CI: -1.20 to -0.61; P < 0.001) and pain score on postoperative day (POD) 1 (SMD = -0.95; 95% CI: -1.54 to -0.36; P = 0.002), POD 2 (SMD = -0.37; 95% CI: -0.63 to -0.11; P = 0.005), and POD 3 (SMD = -0.39; 95% CI: -0.71 to -0.06; P = 0.02). Further subgroup analysis showed that the difference of postoperative LOS became statistically insignificant in the lobectomy or segmentectomy subgroup (SMD = -0.30; 95% CI: -0.91 to 0.32; P = 0.34). Although the risk of pneumothorax was significantly higher in the NT group (RR = 1.75; 95% CI: 1.14–2.68; P = 0.01), the reintervention rates were comparable between groups (RR = 1.04; 95% CI: 0.48–2.25; P = 0.92). No significant difference was found in pleural effusion, subcutaneous emphysema, operation time, pain score on POD 7, and wound healing satisfactory (all P > 0.05). The sensitivity analysis suggested that the results of the meta-analysis were stabilized.

Conclusions

This meta-analysis suggested that NT strategy is safe and feasible for selected patients scheduled for video-assisted thoracoscopic pulmonary resection.

Systematic Review Registration

https://inplasy.com/inplasy-2022-4-0026, identifier INPLASY202240026.
Characterization of the SGLT2 Interaction Network and Its Regulation by SGLT2 Inhibitors: A Bioinformatic Analysis
Authors: Wicik Zofia , Nowak Anna , Jarosz-Popek Joanna , Wolska Marta , Eyileten Ceren , Siller-Matula Jolanta M. , von Lewinski Dirk , Sourij Harald , Filipiak‬ Krzysztof J. , Postuła Marek
Published: August 2022

Background: Sodium–glucose cotransporter 2 (SGLT2), also known as solute carrier family 5 member 2 (SLC5A2), is a promising target for a new class of drugs primarily established as kidney-targeting, effective glucose-lowering agents used in diabetes mellitus (DM) patients. Increasing evidence indicates that besides renal effects, SGLT2 inhibitors (SGLT2i) have also a systemic impact via indirectly targeting the heart and other tissues. Our hypothesis states that the pleiotropic effects of SGLT2i are associated with their binding force, location of targets in the SGLT2 networks, targets involvement in signaling pathways, and their tissue-specific expression.

Methods: Thus, to investigate differences in SGLT2i impact on human organisms, we re-created the SGLT2 interaction network incorporating its inhibitors and metformin and analyzed its tissue-specific expression using publicly available datasets. We analyzed it in the context of the so-called key terms ( autophagy, oxidative stress, aging, senescence, inflammation, AMPK pathways, and mTOR pathways) which seem to be crucial to elucidating the SGLT2 role in a variety of clinical manifestations.

Results: Analysis of SGLT2 and its network components’ expression confidence identified selected organs in the following order: kidney, liver, adipose tissue, blood, heart, muscle, intestine, brain, and artery according to the TISSUES database. Drug repurposing analysis of known SGLT2i pointed out the influence of SGLT1 regulators on the heart and intestine tissue. Additionally, dapagliflozin seems to also have a stronger impact on brain tissue through the regulation of SGLT3 and SLC5A11. The shortest path analysis identified interaction SIRT1-SGLT2 among the top five interactions across six from seven analyzed networks associated with the key terms. Other top first-level SGLT2 interactors associated with key terms were not only ADIPOQ, INS, GLUT4, ACE, and GLUT1 but also less recognized ILK and ADCY7. Among other interactors which appeared in multiple shortest-path analyses were GPT, COG2, and MGAM. Enrichment analysis of SGLT2 network components showed the highest overrepresentation of hypertensive disease, DM-related diseases for both levels of SGLT2 interactors. Additionally, for the extended SGLT2 network, we observed enrichment in obesity (including SGLT1), cancer-related terms, neuroactive ligand–receptor interaction, and neutrophil-mediated immunity.

Conclusion: This study provides comprehensive and ranked information about the SGLT2 interaction network in the context of tissue expression and can help to predict the clinical effects of the SGLT2i.
Traditional chinese medicine in coronary microvascular disease
Authors: Yang Zhihua , Lin Shanshan , Liu Yangxi , Ren Qiuan , Ge Zhao , Wang Ci , Bi Yingfei , Wang Xianliang , Mao Jingyuan
Published: August 2022

Coronary microvascular disease (CMVD) is common in patients with cardiovascular risk factors and is associated with an increased risk of adverse cardiovascular events. Although the study of CMVD in modern medicine is ongoing, there is still no effective treatment for it. Traditional Chinese medicine (TCM) has some clinical advantages based on syndrome differentiation and individualized treatment. In this review, we review the clinical significance, pathogenesis, and current treatments of CMVD and systematically summarize the clinical efficacy and potential action mechanisms of TCM for CMVD. In addition, the scientific problems that need to be solved urgently and the research strategy of TCM for CMVD are described. CMVD has great clinical significance, but there are still many gaps in the related research. This review aims to attract the attention of clinicians to CMVD and promote research on CMVD in TCM.
Dihydromyricetin ameliorates osteogenic differentiation of human aortic valve interstitial cells by targeting c-KIT/interleukin-6 signaling pathway
Authors: Zhang Shaoshao , Fan Leilei , Wang Yongjun , Xu Jianjun , Shen Qiang , Xie Jianhua , Zeng Zhipeng , Zhou Tingwen
Published: August 2022

Aims: Calcific aortic valve disease (CAVD) is a chronic cardiovascular disease with high morbidity that lacks effective pharmacotherapeutics. As a natural flavonoid extracted from Ampelopsis grossedentata, dihydromyricetin (DHM) has been shown to be effective in protecting against atherosclerosis; yet, the therapeutic role of DHM in CAVD remains poorly understood. Herein, we aimed to clarify the therapeutic implications of DHM in CAVD and the underlying molecular mechanisms in human valvular interstitial cells (hVICs).

Methods and Results: The protein levels of two known osteogenesis-specific genes (alkaline phosphatase, ALP; runt-related transcription factor 2, Runx2) and calcified nodule formation in hVICs were detected by Western blot and Alizarin Red staining, respectively. The results showed that DHM markedly ameliorated osteogenic induction medium (OM)–induced osteogenic differentiation of hVICs, as evidenced by downregulation of ALP and Runx2 expression and decreased calcium deposition. The SwissTargetPrediction database was used to identify the potential AVC-associated direct protein target of DHM. Protein–protein interaction (PPI) analysis revealed that c-KIT, a tyrosine-protein kinase, can act as a credible protein target of DHM, as evidenced by molecular docking. Mechanistically, DHM-mediated inhibition of c-KIT phosphorylation drove interleukin-6 (IL-6) downregulation in CAVD, thereby ameliorating OM-induced osteogenic differentiation of hVICs and aortic valve calcification progression.

Conclusion: DHM ameliorates osteogenic differentiation of hVICs by blocking the phosphorylation of c-KIT, thus reducing IL-6 expression in CAVD. DHM could be a viable therapeutic supplement to impede CAVD.
Role of tannic acid against SARS-cov-2 cell entry by targeting the interface region between S-protein-RBD and human ACE2
Authors: Chen Xi , Wang Ziyuan , Wang Jing , Yao Yifan , Wang Qian , Huang Jiahao , Xiang Xianping , Zhou Yifan , Xue Yintong , Li Yan , Gao Xiang , Wang Lijun , Chu Ming , Wang Yuedan
Published: August 2022

Coronavirus disease 2019 (COVID-19) was caused by a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 utilizes human angiotensin converting enzyme 2 (hACE2) as the cellular receptor of its spike glycoprotein (SP) to gain entry into cells. Consequently, we focused on the potential of repurposing clinically available drugs to block the binding of SARS-CoV-2 to hACE2 by utilizing a novel artificial-intelligence drug screening approach. Based on the structure of S-RBD and hACE2, the pharmacophore of SARS-CoV-2-receptor-binding-domain (S-RBD) -hACE2 interface was generated and used to screen a library of FDA-approved drugs. A total of 20 drugs were retrieved as S-RBD-hACE2 inhibitors, of which 16 drugs were identified to bind to S-RBD or hACE2. Notably, tannic acid was validated to interfere with the binding of S-RBD to hACE2, thereby inhibited pseudotyped SARS-CoV-2 entry. Experiments involving competitive inhibition revealed that tannic acid competes with S-RBD and hACE2, whereas molecular docking proved that tannic acid interacts with the essential residues of S-RBD and hACE2. Based on the known antiviral activity and our findings, tannic acid might serve as a promising candidate for preventing and treating SARS-CoV-2 infection.
Reliable reference genes for gene expression analyses under the hypomagnetic field in a migratory insect
Authors: Zhang Ying , Zeng Luying , Wei Yongji , Zhang Ming , Pan Weidong , Sword Gregory A. , Yang Fei , Chen Fajun , Wan Guijun
Published: August 2022

Manipulating the hypomagnetic field (HMF), which is the absence or significant weakening (<5 μT) of the geomagnetic field (GMF), offers a unique tool to investigate magnetic field effects on organismal physiology, development, behavior and life history. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) has been utilized to study changes in gene expression associated with exposure to the HMF. However, selecting appropriate reference genes (RGs) with confirmed stable expression across environments for RT-qPCR is often underappreciated. Using three algorithms (BestKeeper, NormFinder, and GeNorm), we investigated the expression stability of eight candidate RGs when exposed to the HMF condition versus local GMF during developmental from juveniles to adults in the migratory insect pest, the brown planthopper Nilaparvata lugens. During the nymphal stage, RPL5 & α-TUB1, EF1-α & ARF1, RPL5 & AK, EF1-α & RPL5, and ARF1 & AK were suggested as the most stable RG sets in the 1st to 5th instars, respectively. For 1- to 3-day-old adults, AK & ARF1, AK & α-TUB1, AK & ARF1 and EF1-α & RPL5, AK & α-TUB1, AK & EF1-α were the optimal RG sets for macropterous and brachypterous females, respectively. ACT1 & RPL5, RPL5 & EF1-α, α-TUB1 & ACT1 and EF1-α & RPL5, ARF1 & ACT1, ACT1 & ARF1 were the optimal RG sets for macropterous and brachypterous males, respectively. These results will facilitate accurate gene expression analyses under the HMF in N. lugens. The verification approach illustrated in this study highlights the importance of identifying reliable RGs for future empirical studies of magnetobiology (including magnetoreception) that involve magnetic field intensity as a factor.
Research progress on the relationship between autophagy and chronic complications of diabetes
Authors: Ge Xia , Wang Ling , Fei Aihua , Ye Shandong , Zhang Qingping
Published: August 2022

Diabetes is a common metabolic disease whose hyperglycemic state can induce diverse complications and even threaten human health and life security. Currently, the treatment of diabetes is restricted to drugs that regulate blood glucose and have certain accompanying side effects. Autophagy, a research hotspot, has been proven to be involved in the occurrence and progression of the chronic complications of diabetes. Autophagy, as an essential organismal defense mechanism, refers to the wrapping of cytoplasmic proteins, broken organelles or pathogens by vesicles, which are then degraded by lysosomes to maintain the stability of the intracellular environment. Here, we review the relevant aspects of autophagy and the molecular mechanisms of autophagy in diabetic chronic complications, and further analyze the impact of improving autophagy on diabetic chronic complications, which will contribute to a new direction for further prevention and treatment of diabetic chronic complications.
Sirtuins promote brain homeostasis, preventing Alzheimer’s disease through targeting neuroinflammation
Authors: Watroba Mateusz , Szukiewicz Dariusz
Published: August 2022

Both basic pathomechanisms underlying Alzheimer’s disease and some premises for stipulating a possible preventive role of some sirtuins, especially SIRT1 and SIRT3, protective against Alzheimer’s disease-related pathology, are discussed in this article. Sirtuins can inhibit some processes that underlie Alzheimer’s disease-related molecular pathology (e.g., neuroinflammation, neuroinflammation-related oxidative stress, Aβ aggregate deposition, and neurofibrillary tangle formation), thus preventing many of those pathologic alterations at relatively early stages of their development. Subsequently, the authors discuss in details which mechanisms of sirtuin action may prevent the development of Alzheimer’s disease, thus promoting brain homeostasis in the course of aging. In addition, a rationale for boosting sirtuin activity, both with allosteric activators and with NAD+ precursors, has been presented.