bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping the human oral and gut fungal microbiota in patients with metabolic dysfunction-associated fatty liver disease
Authors: Niu Chenguang , Tu Ye , Jin Qiaoqiao , Chen Zhanyi , Yuan Keyong , Wang Min , Zhang Pengfei , Luo Junyuan , Li Hao , Yang Yueyi , Liu Xiaoyu , Mao Mengying , Dong Ting , Tan Wenduo , Hu Xuchen , Pan Yihuai , Hou Lili , Ma Rui , Huang Zhengwei
Published: April 2023

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a phenotype of liver diseases associated with metabolic syndrome. The pathogenesis MAFLD remains unclear. The liver maintains is located near the intestine and is physiologically interdependent with the intestine via metabolic exchange and microbial transmission, underpinning the recently proposed “oral-gut-liver axis” concept. However, little is known about the roles of commensal fungi in the disease development. This study aimed to characterize the alterations of oral and gut mycobiota and their roles in MAFLD. Twenty-one MAFLD participants and 20 healthy controls were enrolled. Metagenomics analyses of saliva, supragingival plaques, and feces revealed significant alterations in the gut fungal composition of MAFLD patients. Although no statistical difference was evident in the oral mycobiome diversity within MAFLD and healthy group, significantly decreased diversities were observed in fecal samples of MAFLD patients. The relative abundance of one salivary species, five supragingival species, and seven fecal species was significantly altered in MAFLD patients. Twenty-two salivary, 23 supragingival, and 22 fecal species were associated with clinical parameters. Concerning the different functions of fungal species, pathways involved in metabolic pathways, biosynthesis of secondary metabolites, microbial metabolism in diverse environments, and carbon metabolism were abundant both in the oral and gut mycobiomes. Moreover, different fungal contributions in core functions were observed between MAFLD patients and the healthy controls, especially in the supragingival plaque and fecal samples. Finally, correlation analysis between oral/gut mycobiome and clinical parameters identified correlations of certain fungal species in both oral and gut niches. Particularly, Mucor ambiguus, which was abundant both in saliva and feces, was positively correlated with body mass index, total cholesterol, low-density lipoprotein, alanine aminotransferase, and aspartate aminotransferase, providing evidence of a possible “oral-gut-liver” axis. The findings illustrate the potential correlation between core mycobiome and the development of MAFLD and could propose potential therapeutic strategies.
Legionella longbeachae wound infection: case report and review of reported Legionella wound infections
Authors: Frostadottir Drifa , Wasserstrom Lisa , Lundén Karolin , Dahlin Lars B.
Published: April 2023

Extrapulmonary manifestations of infection with Legionella species, of which 24 may cause disease in humans, are very rare. Here, we describe a case of a 61-year-old woman with no history of immunosuppression presenting with pain and swelling of her index finger after a prick by rose thorns during gardening. Clinical examination showed fusiform swelling of the finger with mild redness, warmth, and fever. The blood sample revealed a normal white blood cell count and a slight increase in C-reactive protein. Intraoperative observation showed extensive infectious destruction of the tendon sheath, while the flexor tendons were spared. Conventional cultures were negative, while 16S rRNA PCR analysis identified Legionella longbeachae that also could be isolated on buffered charcoal yeast extract media. The patient was treated with oral levofloxacin for 13 days, and the infection healed quickly. The present case report, with a review of the literature, indicates that Legionella species wound infections may be underdiagnosed due to the requirement for specific media and diagnostic methods. It emphasizes the need for heightened awareness of these infections during history taking and clinical examination of patients presenting with cutaneous infections.
Oxygen availability influences the incidence of testicular teratoma in Dnd1Ter/+ mice
Authors: Bustamante-Marin Ximena M. , Capel Blanche
Published: April 2023

Testicular teratomas and teratocarcinomas are the most common testicular germ cell tumors in early childhood and young men, and they are frequently found unilaterally in the left testis. In 129/SvJ mice carrying a heterozygous copy of the potent modifier of tumor incidence Ter, a point mutation in the dead-end homolog one gene (Dnd1Ter/+), ∼70% of the unilateral teratomas arise in the left testis. We previously showed that in mice, left/right differences in vascular architecture are associated with reduced hemoglobin saturation and increased levels of the hypoxia inducible factor-1 alpha (HIF-1α) in the left compared to the right testis. To test the hypothesis that systemic reduction of oxygen availability in Dnd1Ter/+ mice would lead to an increased incidence of bilateral tumors, we placed pregnant females from 129/SvJ Dnd1Ter/+ intercross matings in a hypobaric chamber for 12-h intervals. Our results show that in 129/SvJ Dnd1Ter/+ male gonads, the incidence of bilateral teratoma increased from 3.3% to 64% when fetuses were exposed to acute low oxygen conditions for 12-h between E13.8 and E14.3. The increase in tumor incidence correlated with the maintenance of high expression of pluripotency genes Oct4, Sox2 and Nanog, elevated activity of the Nodal signaling pathway, and suppression of germ cell mitotic arrest. We propose that the combination of heterozygosity for the Ter mutation and hypoxia causes a delay in male germ cell differentiation that promotes teratoma initiation.
Benchmarking microbial DNA enrichment protocols from human intestinal biopsies
Authors: Marchukov Dmitrij , Li Jiaqi , Juillerat Pascal , Misselwitz Benjamin , Yilmaz Bahtiyar
Published: April 2023

Shotgun metagenomic sequencing is a powerful tool for studying bacterial communities in their natural habitats or sites of infection, without the need for cultivation. However, low microbial signals in metagenomic sequencing can be overwhelmed by host DNA contamination, resulting in decreased sensitivity for microbial read detection. Several commercial kits and other methods have been developed to enrich bacterial sequences; however, these assays have not been tested extensively for human intestinal tissues yet. Therefore, the objective of this study was to assess the effectiveness of various wet-lab and software-based approaches for depleting host DNA from microbiome samples. Four different microbiome DNA enrichment methods, namely the NEBNext Microbiome DNA Enrichment kit, Molzym Ultra-Deep Microbiome Prep, QIAamp DNA Microbiome kit, and Zymo HostZERO microbial DNA kit, were evaluated, along with a software-controlled adaptive sampling (AS) approach by Oxford Nanopore Technologies (ONT) providing microbial signal enrichment by aborting unwanted host DNA sequencing. The NEBNext and QIAamp kits proved to be effective in shotgun metagenomic sequencing studies, as they efficiently reduced host DNA contamination, resulting in 24% and 28% bacterial DNA sequences, respectively, compared to <1% in the AllPrep controls. Additional optimization steps using further detergents and bead-beating steps improved the efficacy of less efficient protocols but not of the QIAamp kit. In contrast, ONT AS increased the overall number of bacterial reads resulting in a better bacterial metagenomic assembly with more bacterial contigs with greater completeness compared to non-AS approaches. Additionally, AS also allowed for the recovery of antimicrobial resistance markers and the identification of plasmids, demonstrating the potential utility of AS for targeted sequencing of microbial signals in complex samples with high amounts of host DNA. However, ONT AS resulted in relevant shifts in the observed bacterial abundance, including 2 to 5 times more Escherichia coli reads. Furthermore, a modest enrichment of Bacteroides fragilis and Bacteroides thetaiotaomicron was also observed with AS. Overall, this study provides insight into the efficacy and limitations of various methods for reducing host DNA contamination in human intestinal samples to improve the utility of metagenomic sequencing.
Assessment of miscarriage factors among Latinas who live in the U.S.: a cross-sectional study
Authors: Fernandez-Pineda Madeline , McCabe Brian E. , Cianelli Rosina , Villegas Natalia , Ferrer Lilian , Peragallo Montano Nilda
Published: April 2023

Introduction

Latinas in the US are underrepresented in miscarriage research, yet face several risk factors for having a miscarriage, including intimate partner violence, and increasing maternal age. Increased acculturation is associated to increased risk of intimate partner violence and adverse pregnancy outcomes among Latinas yet is also understudied in the realm of miscarriage. Thus, this study aimed to analyze and compare sociodemographic characteristics, health-related factors, intimate partner violence, and acculturation among Latinas with and without a history of miscarriage.

Methods

This study utilizes a cross-sectional design to analyze baseline data from a randomized clinical trial on the effectiveness of “Salud/Health, Educación/Education, Promoción/Promotion, y/and Autocuidado/Self-care” (SEPA), a human immunodeficiency virus risk reduction intervention for Latinas. Survey interviews were conducted in a private room at the University of Miami Hospital. Survey data analyzed include demographics, a bi-dimensional acculturation scale, a health and sexual health survey, and the hurt, insult, threaten, and scream tool. This study's sample was 296 Latinas, 18 to 50 years old, with and without a history of miscarriage. Data analyses included descriptive statistics, t-tests for continuous variables, negative binomial for counts, and chi-square for dichotomous or categorical variables.

Results

Most Latinas were Cuban (53%), lived in the U.S. an average of 8.4 years, had 13.7 years of education, and a monthly family income of $1,683.56. Latinas with history of miscarriage were significantly older, had more children, more pregnancies, and poorer self-rated health than Latinas without history of miscarriage. Although not significant, a high percentage of intimate partner violence (40%) and low levels of acculturation were reported.

Discussion

This study contributes new data about different characteristics of Latinas who have and have not experienced a miscarriage. Results can help identify Latinas at risk for miscarriage or its adverse-related outcomes and help develop public health policies focusing on preventing and managing miscarriage among Latinas. Further research is warranted to determine the role of intimate partner violence, acculturation, and self-rated health perceptions among Latinas who experience miscarriage. Certified nurse midwives are encouraged to provide Latinas with culturally tailored education on the importance of early prenatal care for optimal pregnancy outcomes.
Crosstalk between oxidative stress and neutrophil response in early ischemic stroke: a comprehensive transcriptome analysis
Authors: Mu Changqing , Wang Yanzhi , Han Chen , Song Hui , Wu Qian , Yang Junyi , Guo Na , Ma Yumei , Zhang Chenguang , Zhang Jian , Liu Xu
Published: April 2023

Background

Ischemic stroke (IS) is the second leading cause of mortality worldwide, continuing to be a serious health concern. It is well known that oxidative stress and neutrophil response play vital roles in the pathophysiology of early IS. However, the complex interactions and critical genes associated with them have not been fully understood.

Methods

Two datasets (GSE37587 and GSE16561) from the Gene Expression Omnibus database were extracted and integrated as the discovery dataset. Subsequent GSVA and WGCNA approaches were used to investigate IS-specific oxidative stress-related genes (ISOSGS). Then, we explored IS-specific neutrophil-associated genes (ISNGS) using CIBERSORT analysis. Next, the protein-protein interaction network was established to ascertain candidate critical genes related with oxidative stress and neutrophil response. Furthermore, these candidate genes were validated using GSE58294 dataset and our clinical samples by RT-qPCR method. Finally, functional annotation, diagnostic capability evaluation and drug-gene interactions were performed by using GSEA analysis, ROC curves and DGIDB database.

Result

In our analysis of discovery dataset, 155 genes were determined as ISOSGS and 559 genes were defined as ISNGS. Afterward, 9 candidate genes were identified through the intersection of ISOSGS and ISNGS, PPI network construction, and filtration by degree algorithm. Then, six real critical genes, including STAT3, MMP9, AQP9, SELL, FPR1, and IRAK3, passed the validation using the GSE58294 dataset and our clinical samples. Further functional annotation analysis indicated these critical genes were associated with neutrophil response, especially neutrophil extracellular trap. Meanwhile, they had a good diagnostic performance. Lastly, 53 potential drugs targeting these genes were predicted by DGIDB database.

Conclusion

We identified 6 critical genes, STAT3, FPR1, AQP9, SELL, MMP9 and IRAK3, related to oxidative stress and neutrophil response in early IS, which may provide new insights into understanding the pathophysiological mechanism of IS. We hope our analysis could help develop novel diagnostic biomarkers and therapeutic strategies for IS.
Systemic therapy with or without transcatheter intra-arterial therapies for unresectable hepatocellular carcinoma: a real-world, multi-center study
Authors: Pan Yangxun , Zhu Xiaodong , Liu Jianwei , Zhong Jianhong , Zhang Wei , Shen Shunli , Jin Renan , Liu Hongzhi , Ye Feng , Hu Kuan , Xu Da , Zhang Yu , Chen Zhong , Xing Baocai , Zhou Ledu , Chen Yongjun , Zeng Yongyi , Liang Xiao , Kuang Ming , Song Tianqiang , Xiang Bangde , Wang Kui , Sun Huichuan , Xu Li ,   China Liver Cancer Study Group Young Investigators (CLEAP)
Published: April 2023

Background

Systemic therapy is the standard care of unresectable hepatocellular carcinoma (uHCC), while transcatheter intra-arterial therapies (TRITs) were also widely applied to uHCC patients in Chinese practice. However, the benefit of additional TRIT in these patients is unclear. This study investigated the survival benefit of concurrent TRIT and systemic therapy used as first-line treatment for patients with uHCC.

Methods

This real-world, multi-center retrospective study included consecutive patients treated at 11 centers accross China between September 2018 and April 2022. Eligible patients had uHCC of China liver cancer stages IIb to IIIb (Barcelona clinic liver cancer B or C stage), and received first-line systemic therapy with or without concurrent TRIT. Of 289 patients included, 146 received combination therapy and 143 received systemic therapy alone. The overall survival (OS), as primary outcomes, was compared between patients who received systemic therapy plus TRIT (combination group) or systemic therapy alone (systemic-only group) using survival analysis and Cox regression. Imbalances in baseline clinical features between the two groups were adjusted through propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). Moreover, subgroup analysis was conducted based on the different tumor characteristics of enrolled uHCC patients.

Results

The median OS was significantly longer in the combination group than the systemic-only group before adjustment [not reached vs. 23.9 months; hazard ratio (HR), 0.561; 95% confidence interval (CI), 0.366 to 0.861; P = 0.008], after PSM (HR, 0.612; 95% CI, 0.390 to 0.958; P = 0.031) and after IPTW (HR, 0.539; 95% CI, 0.116 to 0.961; P = 0.008). Subgroup analyses suggested the benefit of combining TRIT with systemic therapy was greatest in patients with liver tumors exceeding the up-to-seven criteria, with an absence of extrahepatic metastasis, or with alfa-fetoprotein ≥ 400 ng/ml.

Conclusion

Concurrent TRIT with systemic therapy was associated with improved survival compared with systemic therapy alone as first-line treatment for uHCC, especially for patients with high-intrahepatic tumor load and no extrahepatic metastasis.
Construction of a hypoxia-immune-related prognostic panel based on integrated single-cell and bulk RNA sequencing analyses in gastric cancer
Authors: Deng Cuncan , Deng Guofei , Chu Hongwu , Chen Songyao , Chen Xiancong , Li Xing , He Yulong , Sun Chunhui , Zhang Changhua
Published: April 2023

Introduction

Gastric cancer (GC) is the fifth most common tumor, contributing to the third-highest number of cancer-related deaths. Hypoxia is a major feature of the tumor microenvironment. This study aimed to explore the influence of hypoxia in GC and establish a hypoxia-related prognostic panel.

Methods

The GC scRNA-seq data and bulk RNA-seq data were downloaded from the GEO and TCGA databases, respectively. AddModuleScore() and AUCell() were used to calculate module scores and fractions of enrichment for hypoxia-related gene expression in single cells. Least absolute shrinkage and selection operator cox (LASSO-COX) regression analysis was utilized to build a prognostic panel, and hub RNAs were validated by qPCR. The CIBERSORT algorithm was adopted to evaluate immune infiltration. The finding of immune infiltration was validated by a dual immunohistochemistry staining. The TIDE score, TIS score and ESTIMATE were used to evaluate the immunotherapy predictive efficacy.

Results

Hypoxia-related scores were the highest in fibroblasts, and 166 differentially expressed genes were identified. Five hypoxia-related genes were incorporated into the hypoxia-related prognostic panel. 4 hypoxia-related genes (including POSTN, BMP4, MXRA5 and LBH) were significantly upregulated in clinical GC samples compared with the normal group, while APOD expression decreased in GC samples. Similar results were found between cancer-associated fibroblasts (CAFs) and normal fibroblasts (NFs). A high hypoxia score was associated with advanced grade, TNM stage, N stage, and poorer prognosis. Decreased antitumor immune cells and increased cancer-promoting immune cells were found in patients with high hypoxia scores. Dual immunohistochemistry staining showed high expression of CD8 and ACTA2 in gastric cancer tissue. In addition, the high hypoxia score group possessed higher TIDE scores, indicating poor immunotherapy benefit. A high hypoxia score was also firmly related to sensitivity to chemotherapeutic drugs.

Discussion

This hypoxia-related prognostic panel may be effective in predicting the clinical prognosis, immune infiltrations, immunotherapy, and chemotherapy in GC.
Utility of recombinant fusion protein ESAT6-CFP10 skin test for differential diagnosis of active tuberculosis: A prospective study
Authors: Yuan Yuan , Xia Lu , Wu Qiaoyu , Liu Xuhui , Lu Shuihua
Published: April 2023

Background

The recombinant mycobacterium tuberculosis fusion protein ESAT6-CFP10 skin test (ECST) is a novel test for tuberculosis (TB) infection; however, its accuracy in active tuberculosis (ATB) remains uncertain. This study aimed to evaluate the accuracy of ECST in the differential diagnosis of ATB for an early real-world assessment.

Methods

This prospective cohort study recruited patients suspected of ATB in Shanghai Public Health Clinical Center from January 2021 to November 2021. The diagnostic accuracy of the ECST was evaluated under the gold standard and composite clinical reference standard (CCRS) separately. The sensitivity, specificity, and corresponding confidence interval of ECST results were calculated, and subgroup analyses were conducted.

Results

Diagnostic accuracy was analyzed using data from 357 patients. Based on the gold standard, the sensitivity and specificity of the ECST for patients were 72.69% (95%CI 66.8%-78.5%) and 46.15% (95%CI 37.5%-54.8%), respectively. Based on the CCRS, the sensitivity and specificity of the ECST for patients were 71.52% (95%CI 66.4%-76.6%) and 65.45% (95%CI 52.5%-78.4%), respectively. The consistency between the ECST and the interferon-γ release (IGRA) test is moderate (Kappa = 0.47).

Conclusion

The ECST is a suboptimum tool for the differential diagnosis of active tuberculosis. Its performance is similar to IGRA, an adjunctive diagnostic test for diagnosing active tuberculosis.

Clinical trial registration

http://www.chictr.org.cn, identifier ChiCTR2000036369.
A frequent SNP in TRIM5α strongly enhances the innate immune response against LINE-1 elements
Authors: Lagisquet Justine , Conrad Marcus , Wittmann Sabine , Volkmann Bianca , Weissinger Hannah , Sticht Heinrich , Gramberg Thomas
Published: April 2023

The intracellular restriction factor TRIM5α inhibits endogenous LINE-1 retroelements. It induces innate immune signaling cascades upon sensing of cytoplasmic LINE-1 complexes, thereby underlining its importance for protecting the human genome from harmful retrotransposition events. Here, we show that a frequent SNP within the RING domain of TRIM5α, resulting in the variant H43Y, blocks LINE-1 retrotransposition with higher efficiency compared to TRIM5α WT. Upon sensing of LINE-1 complexes in the cytoplasm, TRIM5α H43Y activates both NF-κB and AP-1 signaling pathways more potently than TRIM5α WT, triggering a strong block of the LINE-1 promoter. Interestingly, the H43Y allele lost its antiviral function suggesting that its enhanced activity against endogenous LINE-1 elements is the driving force behind its maintenance within the population. Thus, our study suggests that the H43Y variant of the restriction factor and sensor TRIM5α persists within the human population since it preserves our genome from uncontrolled LINE-1 retrotransposition with higher efficiency.
Guillain-Barré syndrome and COVID-19 vaccines: focus on adenoviral vectors
Authors: Rzymski Piotr
Published: April 2023

COVID-19 vaccination is a life-saving intervention. However, it does not come up without a risk of rare adverse events, which frequency varies between vaccines developed using different technological platforms. The increased risk of Guillain-Barré syndrome (GBS) has been reported for selected adenoviral vector vaccines but not for other vaccine types, including more widely used mRNA preparations. Therefore, it is unlikely that GBS results from the cross-reactivity of antibodies against the SARS-CoV-2 spike protein generated after the COVID-19 vaccination. This paper outlines two hypotheses according to which increased risk of GBS following adenoviral vaccination is due to (1) generation of anti-vector antibodies that may cross-react with proteins involved in biological processes related to myelin and axons, or (2) neuroinvasion of selected adenovirus vectors to the peripheral nervous system, infection of neurons and subsequent inflammation and neuropathies. The rationale behind these hypotheses is outlined, advocating further epidemiological and experimental research to verify them. This is particularly important given the ongoing interest in using adenoviruses in developing vaccines against various infectious diseases and cancer immunotherapeutics.
Portal vein thrombosis in cirrhosis: A literature review
Authors: Prakash Swathi , Bies Jared , Hassan Mariam , Mares Adriana , Didia S. Claudia
Published: April 2023

Portal Vein Thrombosis (PVT), a common complication of advanced liver disease, is defined as an obstruction of the portal vein due to thrombus formation that can extend to the superior mesenteric and splenic veins. It was believed that PVT occurred predominantly due to prothrombotic potential. However, recent studies have shown that decreased blood flow related to portal hypertension appears to increase PVT risk as per Virchow’s triad. It is well known that there is a higher incidence of PVTs in cirrhosis with a higher MELD and Child Pugh score. The controversy for management of PVTs in cirrhotics lies in the individualized assessment of risks versus benefits of anticoagulation, since these patients have a complex hemostatic profile with both bleeding and procoagulant propensities. In this review, we will systematically compile the etiology, pathophysiology, clinical features, and management of portal vein thrombosis in cirrhosis.
Procedural sedation in pediatric dentistry: a narrative review
Authors: Gao Feng , Wu Yujia
Published: April 2023

Procedural sedation and analgesia are now considered standard care for managing pain and anxiety in pediatric dental patients undergoing diagnostic and therapeutic procedures outside of the operating room. Anxiolysis, which combines both pharmacologic and non-pharmacologic approaches, plays a significant role in procedural sedation. Non-pharmacologic interventions such as Behavior Management Technology can help reduce preprocedural agitation, ease the transition to sedation, reduce the required amount of medication for effective sedation, and decrease the occurrence of adverse events. As the introduction of novel sedative regimen and methods in pediatric dentistry, the potential role of mainstay sedatives administered by new routes, for new indications, and with new delivery techniques, should be considered. The purpose of this paper is to examine and discuss the current state of sedation techniques in pediatric dentistry.
Characterization of two multidrug-resistant Klebsiella pneumoniae harboring tigecycline-resistant gene tet(X4) in China
Authors: Yang Yanxian , He Ruowen , Wu Yiping , Qin Mingyang , Chen Jieyun , Feng Yu , Zhao Runping , Xu Lei , Guo Xilong , Tian Guo-Bao , Dai Min , Yan Bin , Qin Li-Na
Published: April 2023

Objectives

Tigecycline is recognized as one of the last-line antibiotics to treat serious bacterial infection caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). The plasmid-borne gene tet(X4) mediates high resistance to tigecycline. However, the prevalence and genetic context of tet(X4) in K. pneumoniae from various sources are not fully understood. Here, we investigated the prevalence of tet(X4)-positive K. pneumoniae and characterized the genetic context of tet(X4)-bearing plasmids in K. pneumoniae isolates.

Methods

Polymerase chain reaction (PCR) was used to detect the tet(X4) gene. The transferability of the tet(X4)-carrying plasmids was tested by conjugation assays. The Galleria mellonella infection model was used to test virulence of tet(X4)-positive strains. Whole-genome sequencing and genome-wide analysis were performed to identify the antimicrobial resistance and the virulence genes, and to clarify the genetic characteristics of the tet(X4)-positive isolates.

Results

Among 921 samples, we identified two tet(X4)-positive K. pneumoniae strains collected from nasal swabs of two pigs (0.22%, 2/921). The two tet(X4)-positive isolates exhibited high minimum inhibitory concentrations to tigecycline (32–256 mg/L) and tetracycline (256 mg/L). The plasmids carrying the tet(X4) gene can transfer from the donor strain K. pneumoniae to the recipient strain Escherichia coli J53. Genetic analysis of the complete sequence of two tet(X4)-carrying plasmids pTKPN_3-186k-tetX4 and pTKPN_8-216k-tetX4 disclosed that the tet(X4) gene was flanked by delta ISCR2 and IS1R, which may mediate the transmission of the tet(X4) gene.

Conclusion

The prevalence of tet(X4)-positive K. pneumoniae among different sources was low. ISCR2 and IS1R may contribute to the horizontal transfer of tet(X4) gene. Effective measures should be taken to prevent the transmission of tet(X4)-producing K. pneumoniae in humans or animals.
Pro- and eukaryotic keystone taxa as potential bio-indicators for the water quality of subtropical Lake Dongqian
Authors: Huang Weihong , Li Shuantong , Li Saisai , Laanbroek Hendrikus J. , Zhang Qiufang
Published: April 2023

The microbial community plays an important role in the biogeochemical cycles in water aquatic ecosystems, and it is regulated by environmental variables. However, the relationships between microbial keystone taxa and water variables, which play a pivotal role in aquatic ecosystems, has not been clarified in detail. We analyzed the seasonal variation in microbial communities and co-occurrence network in the representative areas taking Lake Dongqian as an example. Both pro- and eukaryotic community compositions were more affected by seasons than by sites, and the prokaryotes were more strongly impacted by seasons than the eukaryotes. Total nitrogen, pH, temperature, chemical oxygen demand, dissolved oxygen and chlorophyll a significantly affected the prokaryotic community, while the eukaryotic community was significantly influenced by total nitrogen, ammonia, pH, temperature and dissolved oxygen. The eukaryotic network was more complex than that of prokaryotes, whereas the number of eukaryotic keystone taxa was less than that of prokaryotes. The prokaryotic keystone taxa belonged mainly to Alphaproteobacteria, Betaproteobacteria, Actinobacteria and Bacteroidetes. It is noteworthy that some of the keystone taxa involved in nitrogen cycling are significantly related to total nitrogen, ammonia, temperature and chlorophyll a, including Polaromonas, Albidiferax, SM1A02 and Leptolyngbya so on. And the eukaryotic keystone taxa were found in Ascomycota, Choanoflagellida and Heterophryidae. The mutualistic pattern between pro- and eukaryotes was more evident than the competitive pattern. Therefore, it suggests that keystone taxa could be as bio-indicators of aquatic ecosystems.
Long COVID: Clinical characteristics, proposed pathogenesis and potential therapeutic targets
Authors: Kenny Grace , Townsend Liam , Savinelli Stefano , Mallon Patrick W. G.
Published: April 2023

The emergence of persistent ill-health in the aftermath of SARS-CoV-2 infection has presented significant challenges to patients, healthcare workers and researchers. Termed long COVID, or post-acute sequelae of COVID-19 (PASC), the symptoms of this condition are highly variable and span multiple body systems. The underlying pathophysiology remains poorly understood, with no therapeutic agents proven to be effective. This narrative review describes predominant clinical features and phenotypes of long COVID alongside the data supporting potential pathogenesis of these phenotypes including ongoing immune dysregulation, viral persistence, endotheliopathy, gastrointestinal microbiome disturbance, autoimmunity, and dysautonomia. Finally, we describe current potential therapies under investigation, as well as future potential therapeutic options based on the proposed pathogenesis research.
Role of microglia autophagy and mitophagy in age-related neurodegenerative diseases
Authors: Lin Mingkai , Yu Hongwen , Xie Qiuyan , Xu Zhiyun , Shang Pei
Published: April 2023

Microglia, characterized by responding to damage, regulating the secretion of soluble inflammatory mediators, and engulfing specific segments in the central nervous system (CNS), function as key immune cells in the CNS. Emerging evidence suggests that microglia coordinate the inflammatory responses in CNS system and play a pivotal role in the pathogenesis of age-related neurodegenerative diseases (NDDs). Remarkably, microglia autophagy participates in the regulation of subcellular substances, which includes the degradation of misfolded proteins and other harmful constituents produced by neurons. Therefore, microglia autophagy regulates neuronal homeostasis maintenance and process of neuroinflammation. In this review, we aimed at highlighting the pivotal role of microglia autophagy in the pathogenesis of age-related NDDs. Besides the mechanistic process and the co-interaction between microglia autophagy and different kinds of NDDs, we also emphasized potential therapeutic agents and approaches that could be utilized at the onset and progression of these diseases through modulating microglia autophagy, including promising nanomedicines. Our review provides a valuable reference for subsequent studies focusing on treatments of neurodegenerative disorders. The exploration of microglia autophagy and the development of nanomedicines greatly enhances current understanding of NDDs.
A prediction model of cognitive impairment risk in elderly illiterate Chinese women
Authors: Chen Zhaojing , Du Jiaolan , Song Qin , Yang Jun , Wu Yinyin
Published: April 2023

Objective

To establish and validate a targeted model for the prediction of cognitive impairment in elderly illiterate Chinese women.

Methods

1864 participants in the 2011–2014 cohort and 1,060 participants in the 2014–2018 cohort from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) were included in this study. The Chinese version of the Mini-Mental State Examination (MMSE) was used to measure cognitive function. Demographics and lifestyle information were collected to construct a risk prediction model by a restricted cubic spline Cox regression. The discrimination and accuracy of the model were assessed by the area under the curve (AUC) and the concordance index, respectively.

Results

A total of seven critical variables were included in the final prediction model for cognitive impairment risk, including age, MMSE score, waist-to-height ratio (WHtR), psychological score, activities of daily living (ADL), instrumental abilities of daily living (IADL), and frequency of tooth brushing. The internal and external validation AUCs were 0.8 and 0.74, respectively; and the receiver operating characteristic (ROC) curves indicated good performance ability of the constructed model.

Conclusion

A feasible model to explore the factors influencing cognitive impairment in elderly illiterate women in China and to identify the elders at high risk was successfully constructed.
Gradient adaptive sampling and multiple temporal scale 3D CNNs for tactile object recognition
Authors: Qian Xiaoliang , Meng Jia , Wang Wei , Jiang Liying
Published: April 2023

Tactile object recognition (TOR) is very important for the accurate perception of robots. Most of the TOR methods usually adopt uniform sampling strategy to randomly select tactile frames from a sequence of frames, which will lead to a dilemma problem, i.e., acquiring the tactile frames with high sampling rate will get lots of redundant data, while the low sampling rate will miss important information. In addition, the existing methods usually adopt single time scale to construct TOR model, which will induce that the generalization capability is not enough for processing the tactile data generated under different grasping speeds. To address the first problem, a novel gradient adaptive sampling (GAS) strategy is proposed, which can adaptively determine the sampling interval according to the importance of tactile data, therefore, the key information can be acquired as much as possible when the number of tactile frames is limited. To handle the second problem, a multiple temporal scale 3D convolutional neural networks (MTS-3DCNNs) model is proposed, which downsamples the input tactile frames with multiple temporal scales (MTSs) and extracts the MTS deep features, and the fused features have better generalization capability for recognizing the object grasped with different speed. Furthermore, the existing lightweight network ResNet3D-18 is modified to obtain a MR3D-18 network which can match the tactile data with smaller size and prevent the overfitting problem. The ablation studies show the effectiveness of GAS strategy, MTS-3DCNNs, and MR3D-18 networks. The comprehensive comparisons with advanced methods demonstrate that our method is SOTA on two benchmarks.
Simulation test for impartment of use-dependent plasticity by inactivation of axonal potassium channels on hippocampal mossy fibers
Authors: Zheng Fumeng , Kamiya Haruyuki
Published: April 2023

Modification of axonal excitability directly impacts information transfer through the neuronal networks in the brain. However, the functional significance of modulation of axonal excitability by the preceding neuronal activity largely remains elusive. One remarkable exception is the activity-dependent broadening of action potential (AP) propagating along the hippocampal mossy fibers. The duration of AP is progressively prolonged during repetitive stimuli and facilitated presynaptic Ca2+ entry and subsequent transmitter release. As an underlying mechanism, accumulated inactivation of axonal K+ channels during AP train has been postulated. As the inactivation of axonal K+ channels proceeds on a timescale of several tens of milliseconds slower than the millisecond scale of AP, the contribution of K+ channel inactivation in AP broadening needs to be tested and evaluated quantitatively. Using the computer simulation approach, this study aimed to explore the effects of the removal of the inactivation process of axonal K+ channels in the simple but sufficiently realistic model of hippocampal mossy fibers and found that the use-dependent AP broadening was completely abolished in the model replaced with non-inactivating K+ channels. The results demonstrated the critical roles of K+ channel inactivation in the activity-dependent regulation of axonal excitability during repetitive action potentials, which critically imparts additional mechanisms for robust use-dependent short-term plasticity characteristics for this particular synapse.
The role of RIM in neurotransmitter release: promotion of synaptic vesicle docking, priming, and fusion
Authors: Wu Shanshan , Fan Jiali , Tang Fajuan , Chen Lin , Zhang Xiaoyan , Xiao Dongqiong , Li Xihong
Published: April 2023

There are many special sites at the end of a synapse called active zones (AZs). Synaptic vesicles (SVs) fuse with presynaptic membranes at these sites, and this fusion is an important step in neurotransmitter release. The cytomatrix in the active zone (CAZ) is made up of proteins such as the regulating synaptic membrane exocytosis protein (RIM), RIM-binding proteins (RIM-BPs), ELKS/CAST, Bassoon/Piccolo, Liprin-α, and Munc13-1. RIM is a scaffold protein that interacts with CAZ proteins and presynaptic functional components to affect the docking, priming, and fusion of SVs. RIM is believed to play an important role in regulating the release of neurotransmitters (NTs). In addition, abnormal expression of RIM has been detected in many diseases, such as retinal diseases, Asperger’s syndrome (AS), and degenerative scoliosis. Therefore, we believe that studying the molecular structure of RIM and its role in neurotransmitter release will help to clarify the molecular mechanism of neurotransmitter release and identify targets for the diagnosis and treatment of the aforementioned diseases.
The cost-effectiveness analysis of serplulimab versus regorafenib for treating previously treated unresectable or metastatic microsatellite instability-high or deficient mismatch repair colorectal cancer in China
Authors: Ma Yue , Zhou Jiting , Ye Yuxin , Wang Xintian , Ma Aixia , Li Hongchao
Published: April 2023

Objective

The aim of this study was to investigate the cost-effectiveness of serplulimab versus regorafenib in previously treated unresectable or metastatic microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) colorectal cancer in China.

Methods

From the perspective of China’s health-care system, a Markov model with three health states (progression free, progression, death) was developed for estimating the costs and health outcomes of serplulimab and regorafenib. Data for unanchored matching-adjusted indirect comparison (MAIC), standard parametric survival analysis, the mixed cure model, and transition probabilities calculation were obtained from clinical trials (ASTRUM-010 and CONCUR). Health-care resource utilization and costs were derived from government-published data and expert interviews. Utilities used to calculate quality-adjusted life years (QALYs) were obtained from clinical trials and literature reviews. The primary outcome was the incremental cost-effectiveness ratio (ICER) expressed as cost/QALY gained. Four scenarios were considered in scenario analysis: (a) using original survival data without conducting MAIC; (b) limiting the time horizon to the follow-up time of the clinical trial of serplulimab; (c) adopting a fourfold increase in the risk of death; and (d) applying utilities from two other sources. One-way sensitivity analysis and probabilistic sensitivity analysis were also performed to assess the uncertainty of the results.

Results

In the base-case analysis, serplulimab provided 6.00 QALYs at a cost of $68,722, whereas regorafenib provided 0.69 QALYs at a cost of $40,106. Compared with that for treatment with regorafenib, the ICER for treatment with serplulimab was $5,386/QALY, which was significantly lower than the triple GDP per capita of China in 2021 ($30,036), which was the threshold used to define the cost-effectiveness. In the scenario analysis, the ICERs were $6,369/QALY, $20,613/QALY, $6,037/QALY, $4,783/QALY, and $6,167/QALY, respectively. In the probabilistic sensitivity analysis, the probability of serplulimab being cost-effective was 100% at the threshold of $30,036/QALY.

Conclusion

Compared with regorafenib, serplulimab is a cost-effective treatment for patients with previously treated unresectable or metastatic MSI-H/dMMR colorectal cancer in China.
Recent advances in oncolytic virus therapy for hepatocellular carcinoma
Authors: Zhu Licheng , Lei Yu , Huang Jia , An Yahang , Ren Yanqiao , Chen Lei , Zhao Huangxuan , Zheng Chuansheng
Published: April 2023

Hepatocellular carcinoma (HCC) is a highly refractory cancer and the fourth leading cause of cancer-related mortality worldwide. Despite the development of a detailed treatment strategy for HCC, the survival rate remains unsatisfactory. Oncolytic virus has been extensively researched as a new cancer therapeutic agent in the treatment of HCC. Researchers have designed a variety of recombinant viruses based on natural oncolytic diseases, which can increase the targeting of oncolytic viruses to HCC and their survival in tumors, as well as kill tumor cells and inhibit the growth of HCC through a variety of mechanisms. The overall efficacy of oncolytic virus therapy is known to be influenced by anti-tumor immunity, toxic killing effect and inhibition of tumor angiogenesis, etc. Therefore, a comprehensive review of the multiple oncolytic mechanisms of oncolytic viruses in HCC has been conducted. So far, a large number of relevant clinical trials are under way or have been completed, and some encouraging results have been obtained. Studies have shown that oncolytic virus combined with other HCC therapies may be a feasible method, including local therapy, chemotherapy, molecular targeted therapy and immunotherapy. In addition, different delivery routes for oncolytic viruses have been studied so far. These studies make oncolytic virus a new and attractive drug for the treatment of HCC.
The multistable melanopsins of mammals
Authors: Emanuel Alan J. , Do Michael Tri H.
Published: April 2023

Melanopsin is a light-activated G protein coupled receptor that is expressed widely across phylogeny. In mammals, melanopsin is found in intrinsically photosensitive retinal ganglion cells (ipRGCs), which are especially important for “non-image” visual functions that include the regulation of circadian rhythms, sleep, and mood. Photochemical and electrophysiological experiments have provided evidence that melanopsin has at least two stable conformations and is thus multistable, unlike the monostable photopigments of the classic rod and cone photoreceptors. Estimates of melanopsin’s properties vary, challenging efforts to understand how the molecule influences vision. This article seeks to reconcile disparate views of melanopsin and offer a practical guide to melanopsin’s complexities.
Cannabinoid compounds in combination with curcumin and piperine display an anti-tumorigenic effect against colon cancer cells
Authors: Yüksel Büşra , Hızlı Deniz Ayşen Aslı , Şahin Fikrettin , Sahin Kazim , Türkel Nezaket
Published: April 2023

Currently, use of cannabinoids is limited to improve adverse effects of chemotherapy and their palliative administration during treatment is curiously concomitant with improved prognosis and regressed progression in patients with different tumor types. Although, non-psychoactive cannabidiol (CBD) and cannabigerol (CBG) display antineoplastic effects by repressing tumor growth and angiogenesis both in cell line and animal models, their use as chemotherapeutic agents is awaiting further investigation. Both clinical and epidemiological evidence supported by experimental findings suggest that micronutrients such as curcumin and piperine may present a safer strategy in preventing tumorigenesis and its recurrence. Recent studies demonstrated that piperine potentiates curcumin’s inhibitory effect on tumor progression via enhancing its delivery and therapeutic activity. In this study, we investigated a plausible therapeutic synergism of a triple combination of CBD/CBG, curcumin, and piperine in the colon adenocarcinoma using HCT116 and HT29 cell lines. Potential synergistic effects of various combinations including these compounds were tested by measuring cancer cell proliferation and apoptosis. Our findings revealed that different genetic backgrounds of HCT116 and HT29 cell lines resulted in divergent responses to the combination treatments. Triple treatment showed synergism in terms of exhibiting anti-tumorigenic effects by activating the Hippo YAP signaling pathway in the HCT116 cell line.
Natural compounds ursolic acid and digoxin exhibit inhibitory activities to cancer cells in RORγ-dependent and -independent manner
Authors: Zou Hongye , Yang Yatian , Chen Hong-Wu
Published: April 2023

Natural compounds ursolic acid (UA) and digoxin isolated from fruits and other plants display potent anti-cancer effects in preclinical studies. UA and digoxin have been at clinical trials for treatment of different cancers including prostate cancer, pancreatic cancer and breast cancer. However, they displayed limited benefit to patients. Currently, a poor understanding of their direct targets and mechanisms of action (MOA) severely hinders their further development. We previously identified nuclear receptor RORγ as a novel therapeutic target for castration-resistant prostate cancer (CRPC) and triple-negative breast cancer (TNBC) and demonstrated that tumor cell RORγ directly activates gene programs such as androgen receptor (AR) signaling and cholesterol metabolism. Previous studies also demonstrated that UA and digoxin are potential RORγt antagonists in modulating the functions of immune cells such as Th17 cells. Here we showed that UA displays a strong activity in inhibition of RORγ-dependent transactivation function in cancer cells, while digoxin exhibits no effect at clinically relevant concentrations. In prostate cancer cells, UA downregulates RORγ-stimulated AR expression and AR signaling, whereas digoxin upregulates AR signaling pathway. In TNBC cells, UA but not digoxin alters RORγ-controlled gene programs of cell proliferation, apoptosis and cholesterol biosynthesis. Together, our study reveals for the first-time that UA, but not digoxin, acts as a natural antagonist of RORγ in the cancer cells. Our finding that RORγ is a direct target of UA in cancer cells will help select patients with tumors that likely respond to UA treatment.
Natural products: protective effects against ischemia-induced retinal injury
Authors: He Qianxiong , Xiao Liuyi , Shi Yuanjiang , Li Wanrong , Xin Xiaorong
Published: April 2023

Ischemic retinal damage, a common condition associated with retinal vascular occlusion, glaucoma, diabetic retinopathy, and other eye diseases, threatens the vision of millions of people worldwide. It triggers excessive inflammation, oxidative stress, apoptosis, and vascular dysfunction, leading to the loss and death of retinal ganglion cells. Unfortunately, minority drugs are available for treating retinal ischemic injury diseases, and their safety are limited. Therefore, there is an urgent need to develop more effective treatments for ischemic retinal damage. Natural compounds have been reported to have antioxidant, anti-inflammatory, and antiapoptotic properties that can be used to treat ischemic retinal damage. In addition, many natural compounds have been shown to exhibit biological functions and pharmacological properties relevant to the treatment of cellular and tissue damage. This article reviews the neuroprotective mechanisms of natural compounds involve treating ischemic retinal injury. These natural compounds may serve as treatments for ischemia-induced retinal diseases.