A bat MERS-like coronavirus circulates in pangolins and utilizes human DPP4 and host proteases for cell entry.

It is unknown whether pangolins, the most trafficked mammals, play a role in the zoonotic transmission of bat coronaviruses. We report the circulation of a novel MERS-like coronavirus in Malayan pangolins, named Manis javanica HKU4-related coronavirus (MjHKU4r-CoV). Among 86 animals, four tested positive by pan-CoV PCR, and seven tested seropositive (11 and 12.8%). Four nearly identical (99.9%) genome sequences were obtained, and one virus was isolated (MjHKU4r-CoV-1). This virus utilizes human dipeptidyl peptidase-4 (hDPP4) as a receptor and host proteases for cell infection, which is enhanced by a furin cleavage site that is absent in all known bat HKU4r-CoVs. The MjHKU4r-CoV-1 spike shows higher binding affinity for hDPP4, and MjHKU4r-CoV-1 has a wider host range than bat HKU4-CoV. MjHKU4r-CoV-1 is infectious and pathogenic in human airways and intestinal organs and in hDPP4-transgenic mice. Our study highlights the importance of pangolins as reservoir hosts of coronaviruses poised for human disease emergence.

Identifying SARS-CoV-2-related coronaviruses in Malayan pangolins.

The ongoing outbreak of viral pneumonia in China and across the world is associated with a new coronavirus, SARS-CoV-21. This outbreak has been tentatively associated with a seafood market in Wuhan, China, where the sale of wild animals may be the source of zoonotic infection2. Although bats are probable reservoir hosts for SARS-CoV-2, the identity of any intermediate host that may have facilitated transfer to humans is unknown. Here we report the identification of SARS-CoV-2-related coronaviruses in Malayan pangolins (Manis javanica) seized in anti-smuggling operations in southern China. Metagenomic sequencing identified pangolin-associated coronaviruses that belong to two sub-lineages of SARS-CoV-2-related coronaviruses, including one that exhibits strong similarity in the receptor-binding domain to SARS-CoV-2. The discovery of multiple lineages of pangolin coronavirus and their similarity to SARS-CoV-2 suggests that pangolins should be considered as possible hosts in the emergence of new coronaviruses and should be removed from wet markets to prevent zoonotic transmission.

Comprehensive bioinformatics analysis of human cytomegalovirus pathway genes in pan-cancer.

BACKGROUND: Human cytomegalovirus (HCMV) is a herpesvirus that can infect various cell types and modulate host gene expression and immune response. It has been associated with the pathogenesis of various cancers, but its molecular mechanisms remain elusive. METHODS: We comprehensively analyzed the expression of HCMV pathway genes across 26 cancer types using the Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) databases. We also used bioinformatics tools to study immune invasion and tumor microenvironment in pan-cancer. Cox regression and machine learning were used to analyze prognostic genes and their relationship with drug sensitivity. RESULTS: We found that HCMV pathway genes are widely expressed in various cancers. Immune infiltration and the tumor microenvironment revealed that HCMV is involved in complex immune processes. We obtained prognostic genes for 25 cancers and significantly found 23 key genes in the HCMV pathway, which are significantly enriched in cellular chemotaxis and synaptic function and may be involved in disease progression. Notably, CaM family genes were up-regulated and AC family genes were down-regulated in most tumors. These hub genes correlate with sensitivity or resistance to various drugs, suggesting their potential as therapeutic targets. CONCLUSIONS: Our study has revealed the role of the HCMV pathway in various cancers and provided insights into its molecular mechanism and therapeutic significance. It is worth noting that the key genes of the HCMV pathway may open up new doors for cancer prevention and treatment.

HERVK-mediated regulation of neighboring genes: implications for breast cancer prognosis.

Human endogenous retroviruses (HERVs) are the remnants of ancient retroviral infections integrated into the human genome. Although most HERVs are silenced or rendered inactive by various regulatory mechanisms, they retain the potential to influence the nearby genes. We analyzed the regulatory map of 91 HERV-Ks on neighboring genes in human breast cancer and investigated the impact of HERV-Ks on the tumor microenvironment (TME) and prognosis of breast cancer. Nine RNA-seq datasets were obtained from GEO and NCBI SRA. Differentially expressed genes and HERV-Ks were analyzed using DESeq2. Validation of high-risk prognostic candidate genes using TCGA data. These included Overall survival (multivariate Cox regression model), immune infiltration analysis (TIMER), tumor mutation burden (maftools), and drug sensitivity analysis (GSCA). A total of 88 candidate genes related to breast cancer prognosis were screened, of which CD48, SLAMF7, SLAMF1, IGLL1, IGHA1, and LRRC8A were key genes. Functionally, these six key genes were significantly enriched in some immune function-related pathways, which may be associated with poor prognosis for breast cancer (p = 0.00016), and the expression levels of these genes were significantly correlated with the sensitivity of breast cancer treatment-related drugs. Mechanistically, they may influence breast cancer development by modulating the infiltration of various immune cells into the TME. We further experimentally validated these genes to confirm the results obtained from bioinformatics analysis. This study represents the first report on the regulatory potential of HERV-K in the neighboring breast cancer genome. We identified three key HERV-Ks and five neighboring genes that hold promise as novel targets for future interventions and treatments for breast cancer.

Assessing the effects of tempol on renal fibrosis, inflammation, and oxidative stress in a high-salt diet combined with 5/6 nephrectomy rat model: utilizing oxidized albumin as a biomarker.

BACKGROUND: Oxidative stress has been implicated in the pathogenesis of chronic kidney disease (CKD), prompting the exploration of antioxidants as a potential therapeutic avenue for mitigating disease progression. This study aims to investigate the beneficial impact of Tempol on the progression of CKD in a rat model utilizing oxidized albumin as a biomarker. METHODS: After four weeks of treatment, metabolic parameters, including body weight, left ventricle residual weight, kidney weight, urine volume, and water and food intake, were measured. Systolic blood pressure, urinary protein, oxidized albumin level, serum creatinine (Scr), blood urea nitrogen (BUN), 8-OHdG, TGF-ß1, and micro-albumin were also assessed. Renal fibrosis was evaluated through histological and biochemical assays. P65-NF-κB was quantified using an immunofluorescence test, while Smad3, P65-NF-κB, and Collagen I were measured using western blot. TNF-α, IL-6, MCP-1, TGF-ß1, Smad3, and P65-NF-κB were analyzed by RT-qPCR. RESULTS: Rats in the high-salt diet group exhibited impaired renal function, characterized by elevated levels of blood urea nitrogen, serum creatinine, 8-OHdG, urine albumin, and tubulointerstitial damage, along with reduced body weight. However, these effects were significantly ameliorated by Tempol administration. In the high-salt diet group, blood pressure, urinary protein, and oxidized albumin levels were notably higher compared to the normal diet group, but Tempol administration in the treatment group reversed these effects. Rats in the high-salt diet group also displayed increased levels of proinflammatory factors (TNF-α, IL-6, MCP1) and profibrotic factors (NF-κB activation, Collagen I), elevated expression of NADPH oxidation-related subunits (P65), and activation of the TGF-ß1/Smad3 signaling pathway. Tempol treatment inhibited NF-κB-mediated inflammation and TGF-ß1/Smad3-induced renal fibrosis signaling pathway activation. CONCLUSION: These findings suggest that Tempol may hold therapeutic potential for preventing and treating rats undergoing 5/6 nephrectomy. Further research is warranted to elucidate the mechanisms underlying Tempol's protective effects and its potential clinical applications. Besides, there is a discernible positive relationship between oxidized albumin and other biomarkers, such as 8-OHG, urinary protein levels, mALB, Scr, BUN, and TGF-ß1 in a High-salt diet combined with 5/6 nephrectomy rat model. These findings suggest the potential utility of oxidized albumin as a sensitive indicator for oxidative stress assessment.

Andrographolide inhibits the activation of spinal microglia and ameliorates mechanical allodynia.

Andrographolide (Andro), a labdane diterpene, possesses anti-inflammatory properties and has been used to treat numerous inflammatory diseases. Novel findings revealed that Andro might be vital in regulating pain. However, the contribution of Andro to chronic inflammatory pain has yet to be determined, and its underlying mechanism of action remains unknown. In this study, we observed that Andro attenuated mechanical allodynia in inflammatory pain mice induced by injecting complete Freund's adjuvant (CFA) into the right hind paws. This analgesic effect of Andro is mainly dependent on its inhibition of microglial overactivation and the release of proinflammatory cytokines (TNF and IL-1ß) in lumbar spinal cords of inflammatory pain model mice. More importantly, our data in vivo and in vitro revealed a negative role for Andro in regulating the TLR4/NF-κB signaling pathway, which might contribute to the inhibition of spinal microglial activation and proinflammatory cytokines production, and the improvement of paw withdrawal thresholds in a mouse model of chronic inflammatory pain evoked by CFA. We further found the potential interaction of Andro with TLR4/myeloid differentiation factor 2 heterodimer using molecular modeling, implying that TLR4 might be a potential target for Andro to exert an analgesic effect. Taken together, our findings demonstrated that the modulation of spinal microglial activation by Andro might be substantially conducive to managing chronic pain triggered by neuroinflammation.

Predictive model and risk analysis for coronary heart disease in people living with HIV using machine learning.

OBJECTIVE: This study aimed to construct a coronary heart disease (CHD) risk-prediction model in people living with human immunodeficiency virus (PLHIV) with the help of machine learning (ML) per electronic medical records (EMRs). METHODS: Sixty-one medical characteristics (including demography information, laboratory measurements, and complicating disease) readily available from EMRs were retained for clinical analysis. These characteristics further aided the development of prediction models by using seven ML algorithms [light gradient-boosting machine (LightGBM), support vector machine (SVM), eXtreme gradient boosting (XGBoost), adaptive boosting (AdaBoost), decision tree, multilayer perceptron (MLP), and logistic regression]. The performance of this model was assessed using the area under the receiver operating characteristic curve (AUC). Shapley additive explanation (SHAP) was further applied to interpret the findings of the best-performing model. RESULTS: The LightGBM model exhibited the highest AUC (0.849; 95% CI, 0.814-0.883). Additionally, the SHAP plot per the LightGBM depicted that age, heart failure, hypertension, glucose, serum creatinine, indirect bilirubin, serum uric acid, and amylase can help identify PLHIV who were at a high or low risk of developing CHD. CONCLUSION: This study developed a CHD risk prediction model for PLHIV utilizing ML techniques and EMR data. The LightGBM model exhibited improved comprehensive performance and thus had higher reliability in assessing the risk predictors of CHD. Hence, it can potentially facilitate the development of clinical management techniques for PLHIV care in the era of EMRs.

Characterization and Mapping of a Rolling Leaf Mutant Allele rlT73 on Chromosome 1BL of Wheat.

Leaf rolling is regarded as an important morphological trait in wheat breeding. Moderate leaf rolling is helpful to keep leaves upright and improve the photosynthesis of plants, leading to increased yield. However, studies on the identification of genomic regions/genes associated with rolling leaf have been reported less frequently in wheat. In this study, a rolling leaf mutant, T73, which has paired spikelets, dwarfism, and delayed heading traits, was obtained from a common wheat landrace through ethyl methanesulfonate mutagenesis. The rlT73 mutation caused an increase in the number of epidermal cells on the abaxial side and the shrinkage of bulliform cells on the adaxial side, leading to an adaxially rolling leaf phenotype. Genetic analysis showed that the rolling leaf phenotype was controlled by a single recessive gene. Further Wheat55K single nucleotide polymorphism array-based bulked segregant analysis and molecular marker mapping delimited rlT73 to a physical interval of 300.29-318.33 Mb on the chromosome arm 1BL in the Chinese Spring genome. We show that a point mutation at the miRNA165/166 binding site of the HD zipper class III transcription factor on 1BL altered its transcriptional level, which may be responsible for the rolling leaf phenotype. Our results suggest the important role of rlT73 in regulating wheat leaf development and the potential of miRNA-based gene regulation for crop trait improvement.

Stimuli-Actuated Turn-On Theranostic Nanoplatforms for Imaging-Guided Antibacterial Treatment.

Antibacterial theranostic nanoplatforms, which integrate diagnostic and therapeutic properties, exhibit gigantic application prospects in precision medicine. However, traditional theranostic nanoplatforms usually present an always-on signal output, which leads to poor specificity or selectivity in the treatment of bacterial infections. To address this challenge, stimuli-actuated turn-on nanoplatforms are developed for simultaneous activation of diagnostic signals (e.g., fluorescent, photoacoustic, magnetic signals) and initiation of antibacterial treatment. Specifically, by combining the infection microenvironment-responsive activation of visual signals and antibacterial activity, these theranostic nanoplatforms exert both higher accurate diagnosis rates and more effective treatment effects. In this review, the imaging and treatment strategies that are commonly used in the clinic are first briefly introduced. Next, the recent progress of stimuli-actuated turn-on theranostic nanoplatforms for treating bacterial infectious diseases is summarized in detail. Finally, current bottlenecks and future opportunities of antibacterial theranostic nanoplatforms are also outlined and discussed.

Progress in Pathological and Therapeutic Research of HIV-Related Neuropathic Pain.

HIV-related neuropathic pain (HRNP) is a neurodegeneration that gradually develops during the long-term course of acquired immune deficiency syndrome (AIDS) and manifests as abnormal sock/sleeve-like symmetrical pain and nociceptive hyperalgesia in the extremities, which seriously reduces patient quality of life. To date, the pathogenesis of HRNP is not completely clear. There is a lack of effective clinical treatment for HRNP and it is becoming a challenge and hot spot for medical research. In this study, we conducted a systematic review of the progress of HRNP research in recent years including (1) the etiology, classification and clinical symptoms of HRNP, (2) the establishment of HRNP pathological models, (3) the pathological mechanisms underlying HRNP from three aspects: molecules, signaling pathways and cells, (4) the therapeutic strategies for HRNP, and (5) the limitations of recent HRNP research and the future research directions and prospects of HRNP. This detailed review provides new and systematic insight into the pathological mechanism of HRNP, which establishes a theoretical basis for the future exploitation of novel target drugs. HIV infection, antiretroviral therapy and opioid abuse contribute to the etiology of HRNP with symmetrical pain in both hands and feet, allodynia and hyperalgesia. The pathogenesis involves changes in cytokine expression, activation of signaling pathways and neuronal cell states. The therapy for HRNP should be patient-centered, integrating pharmacologic and nonpharmacologic treatments into multimodal intervention.

Identification and fine-mapping of QYrAS286-2BL conferring adult-plant resistance to stripe rust in cultivated emmer wheat.

KEY MESSAGE: A novel major adult-plant stripe rust resistance QTL derived from cultivated emmer wheat was mapped to a 123.6-kb region on wheat chromosome 2BL. Stripe rust, caused by the fungal pathogen Puccinia striiformis f. sp. tritici (Pst), is one of the most devastating diseases of wheat. Identification of new sources of resistance and their utilization in breeding programs is the effectively control strategy. The objective of this study was to identify and genetically characterize the stripe rust resistance derived from the cultivated emmer accession AS286. A recombinant inbred line population, developed from a cross between the susceptible durum wheat line langdon and AS286, was genotyped using the Wheat55K single nucleotide polymorphism array and evaluated in field conditions with a mixture of the prevalent Chinese Pst races (CYR32, CYR33, CYR34, Zhong4, and HY46) and in growth chamber with race CYR34. Three QTLs conferring resistance were mapped on chromosomes 1BS, 2BL, and 5BL, respectively. The QYrAS286-1BS and QYrAS286-2BL were stable with major effects, explaining 12.91% to 18.82% and 11.31% to 31.43% of phenotypic variation, respectively. QYrAS286-5BL was only detected based on growth chamber seedling data. RILs harboring both QYrAS286-1BS and QYrAS286-2BL showed high levels of stripe rust resistance equal to the parent AS286. The QYrAS286-2BL was only detected at the adult-plant stage, which is different from previously named Yr genes and inherited as a single gene. It was further mapped to a 123.6-kb region using KASP markers derived from SNPs identified by bulked segregant RNA sequencing (BSR-Seq). The identified loci enrich our stripe rust resistance gene pool, and the flanking markers developed here could be useful in marker-assisted selection for incorporating QYrAS286-2BL into wheat cultivars.

Detection of human adenoviruses in influenza-negative patients with respiratory tract infections in Nanning, China.

BACKGROUND: Human adenoviruses (HAdV) have been known to cause a range of diseases, including respiratory tract infections (RTIs). However, there is limited information available regarding the genotype diversity and epidemiology of HAdV associated with RTIs in Nanning. METHODS: Between June 2019 and December 2021, throat swab, nasal swab, or nasopharyngeal swab samples were obtained from individuals hospitalized with respiratory tract infections (RTIs). Statistical software was used to analyze the epidemiological data. The highly conserved 132-bp gene region of the HAdV hexon was targeted for the detection of HAdV using a qPCR assay. An 875-bp hexon gene fragment was subjected to phylogenetic analysis. RESULTS: Significant variations were observed in the age and gender distribution of HAdV-positive patients (P = 0.004 and P = 0.025, respectively). The age distribution of HAdV-positive patients showed that 67.89% of those who tested positive were the age group of 0-6 years. Furthermore, the prevalence of HAdV detection was highest during spring and autumn, with a peak in February. Additionally, genotyping of the 36 HAdV-positive samples with 875-bp fragments identified the presence of circulating HAdV species B, C, and E in Nanning between 2019 and 2021. CONCLUSIONS: This study identified an association between HAdV prevalence and age as well as season. Among hospitalized patients with RTIs in Nanning, HAdV-B, HAdV-C, and HAdV-E were found to be co-circulating. The most commonly detected genotypes were HAdV-C1, HAdV-C6, and HAdV-E4.

Epidemiology of extrapulmonary tuberculosis in central Guangxi from 2016 to 2021.

The burden of extrapulmonary tuberculosis (EPTB) has gradually increased in recent years, but not enough epidemiological data is available from central Guangxi. To better understand the epidemiology of EPTB in central Guangxi and identify risk factors associated with them, we retrospectively investigated the epidemiology of tuberculosis (TB), especially EPTB, among patients admitted to the Chest Hospital of Guangxi Zhuang Autonomous Region between 2016 and 2021. We excluded those infected with both pulmonary tuberculosis (PTB) and EPTB, reported the proportion and incidence of PTB or EPTB, and compared the demographic characteristics and risk factors of EPTB and PTB cases using univariate and multivariate logistic regression models. Among 30,893 TB patients, 67.25% (20,774) had PTB and 32.75% (10,119) had EPTB. Among EPTB, pleural, skeletal, lymphatic, pericardial, meningeal, genitourinary, intestinal, and peritoneal TB accounted for 49.44%, 27.20%, 8.55%, 4.39%, 3.36%, 1.48%, 0.87%, and 0.79%, respectively. Patients who were younger (age < 25), from rural areas, Zhuang and other ethnic groups, and diagnosed with anemia and HIV infection were more likely to develop EPTB. However, patients with diabetes and COPD were less likely to have EPTB. From 2016 to 2021, the proportion of PTB cases decreased from 69.73 to 64.07%. The percentage of EPTB cases increased from 30.27 to 35.93%, with the largest increase in skeletal TB from 21.48 to 34.13%. The epidemiology and risk factors of EPTB in central Guangxi are different from those of PTB. The incidence of EPTB is increasing and further studies are needed to determine the reasons for it.

Open reduction and internal fixation of irreducible displaced femoral neck fracture with femoral Neck System: a preliminary study.

BACKGROUND: Most displaced femoral neck fractures can achieve satisfactory anatomical reduction by closed reduction, but there are still some that cannot reset satisfactorily after closed reduction, and open reduction are required. Such fractures that cannot be repositioned successfully by closed reduction are called irreducible displaced femoral neck fractures in this study. The objective of our study was to evaluate the efficacy of direct anterior incision with the Femoral Neck System in the treatment of irreducible displaced femoral fractures. METHODS: A total of 16 young and middle-aged patients with irreducible displaced femoral neck fractures involving Garden type III and IV were treated using Femoral Neck System fixation by open reduction through Direct Anterior Approach between January 2020 to September 2021. Functional outcomes and postoperative complications were assessed during follow-up. Clinical outcomes were evaluated by the Hip Harris score. The postoperative reduction was evaluated by the Garden Index. Observe postoperative complications. RESULTS: All patients were followed up with a mean follow-up time of 21.1(12-30) months, and according to radiological results, all patients achieved fracture healing, with a mean healing time of 4.25 months. All 16 patients received grade Garden I and II reductions, and there was no significant difference in the anteroposterior Garden reduction index between the first day after surgery (166.13 ± 5.61) and the 12th month after surgery(164.94 ± 4.49) (P>0.05) and no significant difference in lateral Garden index between the first day after surgery(171.06 ± 4.46) and the 12th month after surgery(169.38 ± 3.98) (P<0.05). According to the Hip Harris score scale, 13 patients received excellent and 3 patients received good. The postoperative Hip Harris Score(17.19 ± 4.8) was significantly higher than the preoperative score(92.19 ± 3.4), and the difference was statistically significant (P < 0.05). No or mild femoral neck shortness occurred in 12 (75%) patients, moderate shortening occurred in 3 (18.75%) patients, and severe shortening occurred in 1 (6.25%) patient. None of the patients experienced femoral head necrosis, fracture nonunion, or incision infection. One patient developed deep venous thrombosis of the lower extremity. CONCLUSIONS: The Direct Anterior Approach combined with Femoral Neck System is an excellent treatment for irreducible displaced femoral neck fracture and achieved good functional outcomes and anatomical reduction with low complications.

Pyramiding of Adult-Plant Resistance Genes Enhances All-Stage Resistance to Wheat Stripe Rust.

Stripe rust, caused by Puccinia striiformis f. sp. tritici, is one of the most destructive diseases in wheat production. Pyramiding of adult-plant resistance (APR) genes is a promising strategy to increase durability of resistance. The stripe rust resistance (R) genes Yr18, Yr28, and Yr36 encode different protein families which confer partial resistance to a broad array of P. striiformis f. sp. tritici races. Here, we developed BC3F5 wheat lines representing all possible combinations of Yr18, Yr28, and Yr36 in a genetic background of the highly P. striiformis f. sp. tritici-susceptible wheat line SY95-71 that is widely used in stripe rust analysis. These lines enabled us to accurately evaluate these genes singly and in combination in a common genetic background. The adult plant resistance experiments were analyzed in the field, where stripe rust epidemics occurred frequently. The field results indicated that these partial R genes act additively in enhancing the levels of resistance, and a minimum of two-gene combinations can generate adequate stripe rust resistance. The Yr28 + Yr36 and Yr18 + Yr28 + Yr36 combinations also showed adequate resistance at the seedling stage, implying that APR gene pyramiding can achieve all-stage resistance. Meanwhile, the three genes were simultaneously introduced into elite wheat lines through gene-based marker selection. Elite lines exhibited strong all-stage resistance to stripe rust. This work provides valuable insights and resources for developing durable P. striiformis f. sp. tritici-resistant varieties and for elucidating the regulation mechanism of partial R gene pyramiding.

GRID2 aberration leads to disturbance in neuroactive ligand-receptor interactions via changes to the species richness and composition of gut microbes.

OBJECTIVE: To explore the association between phenotype and the gut microbiome following damage to the GRID2 gene. METHODS: Ten wild-type (WT) mice and 11 GRID2 knockout heterozygous mice (GRID2(±)) of a similar age and weight were randomly selected. Fresh feces were collected from both groups of mice under specified pathogen-free (SPF) conditions. The bacterial genomes were extracted from the feces, the 16S rRNA genes were sequenced, and the data were analyzed to determine clustering, diversity, abundance, LEfSe, and functional differences. Differential expression and enrichment analyses of the RNA-seq and protein levels of the GRID2 gene were also performed using data in the GENE database and the new version of the Human Protein Atlas portal (www.proteinatlas.org). RESULTS: The diversity analysis showed differences in species composition between the two groups at different levels. At phylum level, compared with the WT group, the distribution was more bacteriophages but showed a lower content of Tenericutes in the GRID2(±) group. At the order level, compared with the WT group, a higher content of Actinomycetales and Bacteriophages were found in the GRID2(±) group. The species difference analysis showed that 17 species, including E. faecalis and Paracoccus spp., showed differences in content between the two groups. LEfSe analysis showed that the abundance of Clostridiaceae, Allobaculum, and other groups decreased in the GRID2(±) group compared with the WT group, while Mycoplasma, Sphingomonas, and Alphaproteobacteria increased in abundance. Functional analysis revealed eight differential functions between the WT and GRID2(±) group (P < 0.05). The most significantly disrupted were neuroactive ligand-receptor interactions (P < 9.99e-4). In addition, the differential expression and enrichment analyses performed at RNA-seq and protein levels revealed that the GRID2 gene showed organ-specific expression and was mainly enriched in the brain tissue. CONCLUSIONS: Compared with the WT group, the defective GRID2 gene affected the species richness and composition of gut microbes in the GRID2(±) mice, which in turn affected the function of gut microbes, leading to the disruption of neuroactive ligand-receptor interactions. Our findings indicate that the host gene, GRID2, can influence the abundance of a subset of gut microbes but the exact mechanisms still need further investigation.

Diagnostic value of serum sphingolipids in patients with colorectal cancer.

Background: Abnormal lipid metabolism affects the regulation of tumor progression, though use of serum lipids and sphingolipids for disease progression identification is uncertain. Methods: Serum samples from 51 healthy volunteers and 76 patients were collected and analyzed by liquid chromatography tandem mass spectrometry. Results: Levels of serum total cholesterol and high-density lipoprotein were significantly lower in colorectal cancer patients. Multivariate analysis demonstrated distinct sphingolipid profiles between healthy individuals and patients. Of 106 sphingolipids, 15 metabolites that showed statistical significance were selected, and receiver operating characteristic analysis of these metabolites yielded an area under the curve of 0.868 to 0.9 by machine learning algorithms for distinguishing colorectal cancer from a healthy status. Conclusions: Healthy individuals, polyps patients and colorectal cancer patients have different serum sphingolipid signatures. Serum sphingolipids might be used as biomarkers for early detection or prediction of colorectal cancer.

Anemia and opportunistic infections in hospitalized people living with HIV: a retrospective study.

BACKGROUND: There is a high prevalence of anemia among people living with HIV in Guangxi, China. Therefore, we investigated anemia and opportunistic infections in hospitalized people living with HIV and explored the risk factors related to anemia in people living with HIV to actively prevent anemia in people living with HIV. METHODS: We retrospectively studied people living with HIV admitted to Guangxi Chest Hospital from June 2016 to October 2021. Detailed information on the sociodemographic and clinical features of the participants was collected. The X2 test was used to compare the prevalence between the anemic and non-anemic groups. The logistic regression analysis was applied to exclude confounding factors and identify factors related to anemia. RESULTS: Among 5645 patients with HIV, 1525 (27.02%) had anemia. The overall prevalence of mild, moderate, and severe anemia was 4.66%, 14.08%, and 8.27%, respectively. The factors significantly related to increased risk of anemia were CD4 count < 50 cells/µl (aOR = 2.221, 95% CI = [1.775, 2.779]), CD4 count 50-199 cells/µl (aOR = 1.659, 95% CI = [1.327, 2. 073]), female (aOR = 1.644, 95% CI = [1.436, 1.881]) co-infected with HCV (aOR = 1.465, 95% CI = [1.071, 2.002]), PM (aOR = 2.356, 95% CI = [1.950, 2.849]), or TB (aOR = 1.198, 95% CI = [1.053, 1.365]). CONCLUSIONS: Within Guangxi of China, 27.02% of hospitalized people living with HIV presented with anemia. Most patients with anemia were in the mild to moderate stage. The low CD4 count, female gender, and concomitant infection with Penicillium marneffei, Hepatitis C virus, or Tuberculosis were independent correlates of anemia. Thus, these findings would be helpful to clinicians in preventing and intervening in anemia in people living with HIV.

Immunomodulatory effect of Ganoderma lucidum polysaccharide extract on peritoneal macrophage function of BALB/c mice.

Ganoderma lucidum has been suggested as a natural immunomodulator. It is not yet clear exactly which combination of this extract is responsible for its immunomodulatory effects. Still, it appears that the 3-complement (CR3) receptor on the surface of immune cells acts as a receptor for beta-glucans (glucan-8), which is the main component of this extract. Since glucose-6-phosphate dehydrogenase (G6PD) plays a vital role in regulating macrophage functions, including nitric oxide production, we considered the effect of this extract on viability, G6PD enzyme activity, and nitric oxide (NO) production in peritoneal BALB/c macrophages. First, peritoneal macrophages of BALB/c mice were isolated and treated with concentrations (0.001, 0.01, 0.1, 1, 10, and 100 g/ml) of Ganoderma lucidum polysaccharide extract (GL-PS). After 24 hours of incubation by MTT test, we evaluated the viability of macrophages, and the effective dose was determined to be 0.1g/ml. To determine the specific activity of glucose-6-phosphates, they were incubated with GI-PS for 24 hours at a 0.1 mg/ml dose. Determination of protein concentration was obtained by the Bradford method in cell supernatant extract. Also, after 18 hours of incubation, the amount of nitric oxide (NO) production was measured using Grace colorimetric method. According to the results, a dose of 0.1µg/ml of Ganoderma lucidum polysaccharide extract had the most significant effect on the viability (stimulation coefficient) of peritoneal macrophages compared to other amounts (p <0.05). It was also found that a dose of 0.1µg/ml GL-PS increases NO production and the specific activity of the G6PD enzyme (p <0.05). Ganoderma lucidum, a medicinal fungus, is widely used in East Asian countries, especially in China, to increase the quality of life and longevity. After this study, we concluded that GL-PS extract has an immunomodulatory effect on macrophage activity. Therefore, the polysaccharide extract of this fungus can be used as a strengthening agent of the phagocytic system against infectious agents and pathogens such as the Leishmania parasite because of the production of nitric oxide by macrophages plays an essential role in defense against them.

miR-23b Ameliorates nonalcoholic steatohepatitis by targeting Acyl-CoA thioesterases 4.

Non-alcoholic fatty liver disease (NAFLD) and its more advanced stages, Non-alcoholic steatohepatitis and Cirrhosis, are the most common liver diseases in the worldwide, especially in developing countries. NAFLD is distinguished by the accumulation of triglycerides within hepatocytes. An increasing body of evidence suggests that hepatic MicroRNAs play an important role in NAFLD by controlling lipid metabolism, inflammation, and fibrosis. However, the precise causative functions of miRNA in NAFLD remain unknown. Here, we discovered that mice lacking MicroRNA-23b developed NAFLD-like phenotypes such as increased serum triglyceride and lipid droplet accumulation. In db/db mice fed a high fat diet, MicroRNA-23b overexpression reduced liver weight and alleviated liver inflammation, apoptosis, and fibrosis. MicroRNA-23b regulates the acyl-CoA metabolic process via Acyl-CoA thioesterase 4 (Acot4), which interacts with Acetyl CoA Carboxylase (ACC), according to the RNA-seq analysis.