Ultrasonography screening of hepatic cystic echinococcosis in sheep flocks used for evaluating control progress in a remote mountain area of Hejing County, Xinjiang.

BACKGROUND: Although ultrasonography (US) has been widely used in the diagnosis of human diseases to monitor the progress of cystic echinococcosis (CE) control, the screening method for hepatic CE in sheep flocks requires adjustment. In this study, we used a US scanner to screen sheep flocks and evaluated the efficacy of dosing dogs once a year with praziquantel for 7 years from 2014 to 2021. METHODS: All sheep in the three flocks were screened using an ultrasound scanner in 2014 and compared with the prevalence of infection in 2021 in Bayinbuluke, Xinjiang, China. Sheep age was determined using incisor teeth. Cyst activity and calcification were determined using US images. The dogs were dewormed with praziquantel once a year to control echinococcosis in the community. RESULTS: Three flocks had 968 sheep in 2014, with 13.22%, 22.62%, 18.7%, 27.27%, 11.88%, and 6.3% of sheep aged 1, 2, 3, 4, 5, and ≥ 6 years old, respectively. US scanning revealed that the overall CE prevalence was 38.43% (372/968), with active cysts and calcified cysts present in 9.40% (91/968) and 29.02% (281/968) of the sheep, respectively. For the young sheep aged 1 and 2 years, the prevalence of active and calcified cysts was: 1.56% and 0.91%, and 10.94% and 18.72%, respectively. Approximately 15.15% and 16.52% of the 4- and 5-year-old sheep, respectively, harbored active cysts. There was no significant difference in the infection rates of sheep between 2014 and 2021 (P > 0.05). CONCLUSIONS: US is a practical tool for the field screening of CE in sheep flocks. One-third of the sheep population in the flocks was 1-2 years old, and these sheep played a very limited role in CE transmission, as most of the cysts were calcified. Old sheep, especially culled aged sheep, play a key role in the transmission of CE. Dosing dogs once a year did not affect echinococcosis control.

The prognostic value and immunological role of MVP in pan-cancer study.

Major Vault Protein (MVP) has emerged as a potential prognostic and immunological biomarker in various cancer types. This pan-cancer study aimed to investigate expression of MVP and its correlation with clinical outcomes and immune infiltration across diverse cancer types. We conducted an analysis of extensive transcriptomic and clinical data from publicly available databases. Our findings unveiled a significant association between MVP expression and cancer progression, with higher expression levels predicting poorer overall survival in multiple cancer types. Importantly, MVP expression demonstrated a close relationship with immune infiltration in the tumor microenvironment, showing that higher expression levels were associated with increased immune cell infiltration. We further validated expression of MVP and function in cancer cell lines A549 and AGS. These compelling results suggest that MVP holds promise as a valuable biomarker for prognostic assessment and the development of immunotherapeutic strategies across various cancer types. Consequently, targeting MVP may offer a compelling therapeutic approach in the treatment of human cancers.

SIRT3 alleviates painful diabetic neuropathy by mediating the FoxO3a-PINK1-Parkin signaling pathway to activate mitophagy.

INTRODUCTION: Painful diabetic neuropathy (PDN) is a common complication of diabetes. Previous studies have implicated that mitochondrial dysfunction plays a role in the development of PDN, but its pathogenesis and mechanism have not been fully investigated. METHODS: In this study, we used high-fat diet/low-dose streptozotocin-induced rats as a model of type 2 diabetes mellitus. Behavioral testing, whole-cell patch-clamp recordings of dorsal root ganglion (DRG) neurons, and complex sensory nerve conduction velocity studies were used to assess peripheral neuropathy. Mitochondrial membrane potential (MMP), ATP, tissue reactive oxygen species, and transmission electron microscopy were used to evaluate the function and morphology of mitochondria in DRG. Real-time PCR, western blot, and immunofluorescence were performed to investigate the mechanism. RESULTS: We found that damaged mitochondria were accumulated and mitophagy was inhibited in PDN rats. The expression of sirtuin 3 (SIRT3), which is an NAD+-dependent deacetylase in mitochondria, was inhibited. Overexpression of SIRT3 in DRG neurons by intrathecally administered LV-SIRT3 lentivirus ameliorated neurological and mitochondrial dysfunctions. This was evidenced by the reversal of allodynia and nociceptor hyperexcitability, as well as the restoration of MMP and ATP levels. Overexpression of SIRT3 restored the inhibited mitophagy by activating the FoxO3a-PINK1-Parkin signaling pathway. The effects of SIRT3 overexpression, including the reversal of allodynia and nociceptor hyperexcitability, the improvement of impaired mitochondria and mitophagy, and the restoration of PINK1 and Parkin expression, were counteracted when FoxO3a siRNA was intrathecally injected. CONCLUSION: These results showed that SIRT3 overexpression ameliorates PDN via activation of FoxO3a-PINK1-Parkin-mediated mitophagy, suggesting that SIRT3 may become an encouraging therapeutic strategy for PDN.

Is redox zonation an appropriate method for determining the stage of natural remediation in deep contaminated groundwater?

Groundwater contamination resulting from petroleum development poses a significant threat to drinking water sources, especially in developing countries. In situ natural remediation methods, including microbiological processes, have gained popularity for the reduction of groundwater contaminants. However, assessing the stage of remediation in deep contaminated groundwater is challenging and costly due to the complexity of diverse geological conditions and unknown initial concentrations of contaminants. This research proposes that redox zonation may be a more convenient and comprehensive indicator than the concentration of contaminants for determining the stage of natural remediation in deep groundwater. The combination of sequencing microbial composition using the high-throughput 16S rRNA gene and function predicted by FAPROTAX is a useful approach to determining the redox conditions of different contaminated groundwater. The sulfate-reducing environment, represented by Desulfobacteraceae, Peptococcaceae, Desulfovibrionaceae, and Desulfohalobiaceae could be used as characteristic early stages of remediation for produced water contamination in wells with high concentrations of SO42-, benzene, and salinity. The nitrate-reducing environment, enriched with microorganisms related to denitrification, sulfur-oxidizing, and methanophilic microorganisms could be indicative of the mid stages of in situ bioremediation. The oxygen reduction environment, enriched with oligotrophic and pathogenic Sphingomonadaceae, Caulobacteraceae, Syntrophaceae, Legionellales, Moraxellaceae, and Coxiellaceae, could be indicative of the late stages of remediation. This comprehensive approach could provide valuable insights into the process of natural remediation and facilitate improved environmental management in areas of deep contaminated groundwater.

Factors Associated With Radiological Lung Growth Rate After Lobectomy in Patients With Lung Cancer.

INTRODUCTION: This study is a retrospective study. This study aims to explore the association between lobectomy in lung cancer patients and subsequent compensatory lung growth (CLG), and to identify factors that may be associated with variations in CLG. METHODS: 207 lung cancer patients who underwent lobectomy at Yunnan Cancer Hospital between January 2020 and December 2020. All patients had stage IA primary lung cancer and were performed by the same surgical team. And computed tomography examinations were performed before and 1 y postoperatively. Based on computed tomography images, the volume of each lung lobe was measured using computer software and manual, the radiological lung weight was calculated. And multiple linear regressions were used to analyze the factors related to the increase in postoperative lung weight. RESULTS: One year after lobectomy, the radiological lung weight increased by an average of 112.4 ± 20.8%. Smoking history, number of resected lung segments, preoperative low attenuation volume, intraoperative arterial oxygen partial pressure/fraction of inspired oxygen ratio and postoperative visual analog scale scores at 48 h were significantly associated with postoperative radiological lung weight gain. CONCLUSIONS: Our results suggest that CLG have occurred after lobectomy in adults. In addition, anesthetists should maintain high arterial oxygen partial pressure/fraction of inspired oxygen ratio during one-lung ventilation and improve acute postoperative pain to benefit CLG.

Enhancing metformin-induced tumor metabolism destruction by glucose oxidase for triple-combination therapy.

Despite decades of laboratory and clinical trials, breast cancer remains the main cause of cancer-related disease burden in women. Considering the metabolism destruction effect of metformin (Met) and cancer cell starvation induced by glucose oxidase (GOx), after their efficient delivery to tumor sites, GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in situ. Herein, a pH-responsive epigallocatechin gallate (EGCG)-conjugated low-molecular-weight chitosan (LC-EGCG, LE) nanoparticle (Met-GOx/Fe@LE NPs) was constructed. The coordination between iron ions (Fe3+) and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton reaction. Met-GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its stability. Moreover, this pH-responsive nanoplatform presents controllable drug release behavior. An in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nanoplatform was 3.6-fold higher than that of the free drug. The in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their proliferation. This triple-combination therapy approach is promising for efficient and targeted cancer treatment.

A novel member of drug/metabolite transporter (DMT) family efflux pump, SA00565, contributes to tetracycline antibiotics resistance in Staphylococcus aureus USA300.

Drug efflux systems have recently been recognized as a significant mechanism responsible for multidrug resistance in bacteria. In this study, we described the identification and characterization of a new chromosomally encoded efflux pump (SA00565) in Staphylococcus aureus. SA00565, which belongs to the drug/metabolite transporter (DMT) superfamily, was predicted to be a 10-transmembrane segment transporter. To evaluate the role of sa00565 in resistance, we generated sa00565 gene deletion mutant (Δsa00565) and assessed its susceptibility to 35 different antibiotic treatments. Our results demonstrated that the Δsa00565 mutant exhibited reduced resistance to tetracycline and doxycycline, with 64-fold and 12-fold decreased MICs, respectively. The mechanism of SA00565-mediated tetracycline resistance was demonstrated that SA00565 possesses the capability to efficiently extrud intracellular tetracycline into the environment. The efflux activity of SA00565 was further validated using EtBr accumulation and efflux assays. In summary, our study uncovered a previously unknown function of a DMT family transporter, which serves as a tetracycline efflux pump, thereby contributing to tetracycline resistance in S. aureus.IMPORTANCEIn this study, we addressed the significance of drug efflux systems in multidrug resistance of Staphylococcus aureus, focusing on the unexplored efflux pump SA00565 in the drug/metabolite transporter (DMT) superfamily. Through phylogenetic analysis, gene knockout, and overexpression experiments, we identified the role of SA00565 in antibiotic resistance. The Δsa00565 mutant showed increased susceptibility to tetracycline and doxycycline in disk diffusion assays, with significantly lower MICs compared to the WT. Remarkably, intracellular tetracycline concentration in the mutant was two- to threefold higher, indicating SA00565 actively eliminates intracellular tetracycline. Our findings emphasize the pivotal contribution of SA00565 to tetracycline antibiotic resistance in S. aureus, shedding light on its functional attributes within the DMT superfamily and providing valuable insights for combating multidrug resistance.

Pd-Adsorbed SiN3 Monolayer as a Promising Gas Scavenger for SF6 Partial Discharge Decomposition Components: Insights from the First-Principles Study.

Gas-insulated switchgear (GIS) equipment must be protected by detecting and eliminating the toxic SF6 partial discharge decomposition components. This study employs first-principles calculations to thoroughly investigate the interaction between a Pd-adsorbed SiN3 monolayer (Pd-SiN3) and four typical SF6 decomposition gases (H2S, SO2, SOF2, and SO2F2). The study also investigates the associated geometric, electrical, and optical characteristics along with the sensing sensitivity and desorption efficiency. The ab initio molecular dynamics (AIMD) simulations demonstrated the favorable stability of the Pd-SiN3 monolayer. Furthermore, the Pd-SiN3 monolayer exhibited strong chemisorption behavior toward H2S, SO2, SOF2, and SO2F2 gases because of the higher adsorption energies of -2.717, -2.917, -2.457, and -2.025 eV, respectively. Furthermore, significant changes occur in the electronic and optical characteristics of the Pd-SiN3 monolayer following the adsorption of these gases, resulting in remarkable sensitivity of the Pd-SiN3 monolayer in relation to electrical conductivity and optical absorption. Meanwhile, all of these gas adsorption systems exhibited extremely long recovery times. The aforementioned theoretical findings suggest that the Pd-SiN3 monolayer has the potential to be an effective gas scavenger for the storage or removal of the SF6 decomposition components. Additionally, it might function as a reliable one-time sensor for detecting these gases. The results potentially provide valuable theoretical guidance for maintaining the normal operation of the SF6 insulation devices.

Thiosulfate/FeCl3 pre-treatment enhances short-chain fatty acid production and mitigates H2S generation during anaerobic fermentation of waste activated sludge: Performance, microbial community and ecological analyses.

Anaerobic fermentation (AF) has been identified as a promising method of transforming waste activated sludge (WAS) into high-value products (e.g., short-chain fatty acids (SCFAs)). This study developed thiosulfate/FeCl3 pre-treatment and investigated the effects of different thiosulfate/FeCl3 ratios (S:Fe = 3:1, 3:2, 1:1, 3:4 and 3:5) on SCFA production and sulfur transformation during the AF of WAS. At a S:Fe ratio of 1:1, the maximal SCFA yield (933.3 mg COD/L) and efficient H2S removal (96.5 %) were obtained. S:Fe ratios ≤ 1:1 not only benefited hydrolysis and acidification but largely mitigated H2S generation. These results were supported by the enriched acidogens and reduced sulfur-reducing bacteria (SRB). Molecular ecological network analysis further revealed that the keystone taxon (g_Saccharimonadales) was found in S:Fe = 1:1, together with reductions in associations among methanogens, acidogens and SRB. This work provides a strategy for enhancing high-value product recovery from WAS and minimising H2S emissions.

Association of anti-Müllerian hormone and insulin resistance in adolescent girls with polycystic ovary syndrome.

INTRODUCTION: Insulin resistance (IR) is confirmed as an important feature among polycystic ovary syndrome (PCOS) patients. Anti-Müllerian hormone (AMH), a vital marker of ovarian dysfunction, is proposed for inclusion in the diagnosis of PCOS in adolescents. We sought to investigate the relationship between the AMH level and IR in Chinese girls with PCOS. MATERIAL AND METHODS: 92 girls with PCOS aged 14-18 years were enrolled and divided into 2 subgroups: PCOS with IR group (n = 25) and PCOS without IR group (n = 67). A homeostasis model assessment-insulin resistance (HOMA-IR) value ≥ 2.5 was defined as IR. Clinical data and biochemical indexes were compared between the 2 groups. Multivariate logistic regression analysis and multivariate linear regression analysis were performed to determine which clinical variables were independently associated with IR and AMH level, respectively. RESULTS: PCOS girls with IR had higher levels of AMH than those of PCOS girls without IR (p < 0.01). Moreover, body mass index, triglyceride, and AMH values were shown to be independent risk factors for HOMA-IR after multivariate analysis. Meanwhile, age, insulin, and follicle-stimulating hormone levels were significantly related to AMH levels in those girls. CONCLUSIONS: Our findings show that AMH is an independent determinant of IR in PCOS adolescents, and the fasting insulin level is closely associated with the AMH level, which indicates that the AMH pathway might play a role in the development of IR in PCOS adolescents. The interaction between AMH and IR in PCOS girls warrants further large-scale evaluation.

Comparative transcriptomic evidence of physiological changes and potential relationships in vertebrates under different dormancy states.

Dormancy represents a fascinating adaptive strategy for organisms to survive in unforgiving environments. After a period of dormancy, organisms often exhibit exceptional resilience. This period is typically divided into hibernation and aestivation based on seasonal patterns. However, the mechanisms by which organisms adapt to their environments during dormancy, as well as the potential relationships between different states of dormancy, deserve further exploration. Here, we selected Perccottus glenii and Protopterus annectens as the primary subjects to study hibernation and aestivation, respectively. Based on histological and transcriptomic analysis of multiple organs, we discovered that dormancy involved a coordinated functional response across organs. Enrichment analyses revealed noteworthy disparities between the two dormant species in their responses to extreme temperatures. Notably, similarities in gene expression patterns pertaining to energy metabolism, neural activity, and biosynthesis were noted during hibernation, suggesting a potential correlation between hibernation and aestivation. To further explore the relationship between these two phenomena, we analyzed other dormancy-capable species using data from publicly available databases. This comparative analysis revealed that most orthologous genes involved in metabolism, cell proliferation, and neural function exhibited consistent expression patterns during dormancy, indicating that the observed similarity between hibernation and aestivation may be attributable to convergent evolution. In conclusion, this study enhances our comprehension of the dormancy phenomenon and offers new insights into the molecular mechanisms underpinning vertebrate dormancy.

Genetic background of hematological parameters in Holstein cattle based on genome-wide association and RNA sequencing analyses.

Hematological parameters refer to the assessment of changes in the number and distribution of blood cells, including leukocytes (LES), erythrocytes (ERS), and platelets (PLS), which are essential for the early diagnosis of hematological system disorders and other systemic diseases in livestock. In this context, the primary objectives of this study were to investigate the genomic background of 19 hematological parameters in Holstein cattle, focusing on LES, ERS, and PLS blood components. Genetic and phenotypic (co)variances of hematological parameters were calculated based on the Average Information Restricted Maximum Likelihood (AIREML) method and 1,610 genotyped individuals and 5,499 hematological parameter records from 4,543 cows. Furthermore, we assessed the genetic relationship between these hematological parameters and other economically important traits in dairy cattle breeding programs. We also carried out genome-wide association studies and candidate gene analyses. Blood samples from 21 primiparous cows were used to identify candidate genes further through RNA sequencing (RNA-seq) analyses. Hematological parameters generally exhibited low-to-moderate heritabilities ranging from 0.01 to 0.29, with genetic correlations between them ranging from -0.88 ± 0.09 (between mononuclear cell ratio and lymphocyte cell ratio) to 0.99 ± 0.01 (between white blood cell count and granulocyte cell count). Furthermore, low to moderate approximate genetic correlations between hematological parameters with one longevity, 4 fertility, and 5 health traits were observed. One-hundred-and-99 significant single nucleotide polymorphisms (SNP) located primarily on the Bos taurus autosomes (BTA) BTA4, BTA6, and BTA8 were associated with 16 hematological parameters. Based on the RNA-seq analyses, 6,687 genes were significantly downregulated and 4,119 genes were upregulated when comparing 2 groups of cows with high and low phenotypic values. By integrating genome-wide association studies (GWAS), RNA-seq, and previously published results, the main candidate genes associated with hematological parameters in Holstein cattle were ACRBP, ADAMTS3, CANT1, CCM2L, CNN3, CPLANE1, GPAT3, GRIP2, PLAGL2, RTL6, SOX4, WDFY3, and ZNF614. Hematological parameters are heritable and moderately to highly genetically correlated among themselves. The large number of candidate genes identified based on GWAS and RNA-seq indicate the polygenic nature and complex genetic determinism of hematological parameters in Holstein cattle.

Activation of CRF/CRFR1 Signaling in the Central Nucleus of the Amygdala Contributes to Chronic Stress-Induced Exacerbation of Neuropathic Pain by Enhancing GluN2B-NMDA Receptor-Mediated Synaptic Plasticity in Adult Male Rats.

Exacerbation of pain by chronic stress and comorbidity of pain with stress-related disorders such as depression and post-traumatic stress disorder, represent significant clinical challenges. Previously we have documented that chronic forced swim (FS) stress exacerbates neuropathic pain in spared nerve injury (SNI) rats, associated with an up-regulation of GluN2B-containing N-methyl-D-aspartate receptors (GluN2B-NMDARs) in the central nucleus of the amygdala (CeA). However, the molecular mechanisms underlying chronic FS stress (CFSS)-mediated exacerbation of pain sensitivity in SNI rats still remain unclear. In this study, we demonstrated that exposure of CFSS to rats activated the corticotropin-releasing factor (CRF)/CRF receptor type 1 (CRFR1) signaling in the CeA, which was shown to be necessary for CFSS-induced depressive-like symptoms in stressed rats, and as well, for CFSS-induced exacerbation of pain hypersensitivity in SNI rats exposed to chronic FS stress. Furthermore, we discovered that activation of CRF/CRFR1 signaling in the CeA upregulated the phosphorylation of GluN2B-NMDARs at tyrosine 1472 (pGluN2BY1472) in the synaptosomal fraction of CeA, which is highly correlated to the enhancement of synaptic GluN2B-NMDARs expression that has been observed in the CeA in CFSS-treated SNI rats. In addition, we revealed that activation of CRF/CRFR1 signaling in the CeA facilitated the CFSS-induced reinforcement of long-term potentiation as well as the enhancement of NMDAR-mediated excitatory postsynaptic currents in the basolateral amygdala (BLA)-CeA pathway in SNI rats. These findings suggest that activation of CRF/CRFR1 signaling in the CeA contributes to chronic stress-induced exacerbation of neuropathic pain by enhancing GluN2B-NMDAR-mediated synaptic plasticity in rats subjected to nerve injury. PERSPECTIVE: Our present study provides a novel mechanism for elucidating stress-induced hyperalgesia and highlights that the CRF/CRFR1 signaling and the GluN2B-NMDAR-mediated synaptic plasticity in the CeA may be important as potential therapeutic targets for chronic stress-induced pain exacerbation in human neuropathic pain. DATA AVAILABILITY: The data that support the findings of this study are available from the corresponding author upon reasonable request.

NDC1 promotes hepatocellular carcinoma tumorigenesis by targeting BCAP31 to activate PI3K/AKT signaling.

Hepatocellular carcinoma (HCC) is among the world's worst malignancies. Nuclear division cycle 1 (NDC1) is an essential membrane-integral nucleoporin, found in this study to be significantly increased in primary HCC. A multivariate analysis revealed that higher NDC1 expression was linked to worse outcome in HCC patients. Mouse xenograft tumors overexpressing NDC1 grew rapidly, and HCC cells overexpressing NDC1 showed enhanced proliferation, invasion, and migration in vitro. In contrast, knocking down NDC1 had the opposite effects in vitro. Furthermore, co-immunoprecipitation and liquid chromatograph mass spectrometer analyses revealed that NDC1 activated PI3K/AKT signaling by interacting with BCAP31. In summary, NDC1 and BCAP31 cooperate to promote the PI3K/AKT pathway, which is essential for HCC carcinogenesis. This suggests that NDC1 is predictive of prognosis in HCC.

Intestinal Colonized Silkworm Chrysalis-Like Probiotic Composites for Multi-Crossed Comprehensive Synergistic Therapy of Inflammatory Bowel Disease.

Inspired by the timely emergence of silkworm pupae from their cocoons, silkworm chrysalis-like probiotic composites (SCPCs) are developed for the comprehensive therapy of inflammatory bowel disease (IBD), in which probiotics are enveloped as the "pupa" in a sequential layering of silk sericin (SS), tannic acid (TA), and polydopamine, akin to the protective "cocoon". Compared to unwrapped probiotics, these composites not only demonstrate exceptional resistance to the harsh gastrointestinal environment and exhibit over 200 times greater intestinal colonization but also safeguard probiotics from the damage of IBD environment while enabling probiotics sustained release. The probiotics, in synergy with SS and TA, provide a multi-crossed comprehensive therapy for IBD that simultaneously addresses various pathological features of IBD, including intestinal barrier disruption, elevated pro-inflammatory cytokines, heightened oxidative stress, and disturbances in the intestinal microbiota. SCPCs exhibit remarkable outcomes, including a 9.7-fold reduction in intestinal permeability, an 8.9-fold decrease in IL-6 levels, and a 2.9-fold reduction in TNF-α levels compared to uncoated probiotics. Furthermore, SCPCs demonstrate an impressive 92.25% reactive oxygen species clearance rate, significantly enhance the richness of beneficial intestinal probiotics, and effectively diminish the abundance of pathogenic bacteria, indicating a substantial improvement in the overall therapeutic effect of IBD.

Ruthenium-dihydroartemisinin complex: a promising new compound for colon cancer prevention via G1 cell cycle arrest, apoptotic induction, and adaptive immune regulation.

BACKGROUND: Artemisinin (ART) and its derivatives are important antimalaria agents and have received increased attention due to their broad biomedical effects, such as anticancer and anti-inflammation activities. Recently, ruthenium-derived complexes have attracted considerable attention as their anticancer potentials were observed in preclinical and clinical studies. METHODS: To explore an innovative approach in colorectal cancer (CRC) management, we synthesized ruthenium-dihydroartemisinin complex (D-Ru), a novel metal-based artemisinin derivative molecule, and investigated its anticancer, anti-inflammation, and adaptive immune regulatory properties. RESULTS: Compared with its parent compound, ART, D-Ru showed stronger antiproliferative effects on the human CRC cell lines HCT-116 and HT-29. The cancer cell inhibition of D-Ru comprised G1 cell cycle arrest via the downregulation of cyclin A and the induction of apoptosis. ART and D-Ru downregulated the expressions of pro-inflammatory cytokines IL-1ß, IL-6, and IL-8. Although ART and D-Ru did not suppress Treg cell differentiation, they significantly inhibited Th1 and Th17 cell differentiation. CONCLUSIONS: Our results demonstrated that D-Ru, a novel ruthenium complexation of ART, remarkably enhanced its parent compound's anticancer action, while the anti-inflammatory potential was not compromised. The molecular mechanisms of action of D-Ru include inhibition of cancer cell growth via cell cycle arrest, induction of apoptosis, and anti-inflammation via regulation of adaptive immunity.

Effects of biotin and coated cobalamin on lactation performance, nutrient digestion and rumen fermentation in Holstein dairy cows.

Biotin (BI) and cobalamin (CA) are essential for rumen propionate production and hepatic gluconeogenesis. The study evaluated the influence of BI or/and coated CA (CCA) on milk performance and nutrient digestion in cows. Sixty Holstein dairy cows were assigned in a 2 × 2 factorial arrangement and randomised block design to four groups. The factors were BI at 0 or 20 mg/day and CCA at 0 or 9 mg CA/day. Dry matter intake increased with BI addition but was unchanged with CCA supply. Addition of BI or CCA increased fat-corrected milk, milk fat and milk protein yields and feed efficiency. Moreover, lactose yield was increased by CCA addition. Dry matter, organic matter, crude protein and acid detergent fibre total-tract digestibility increased for BI or CCA supply. When CCA was supplemented, positive response of neutral detergent fibre digestibility to BI addition was enhanced. Supplementing BI did not affect pH, propionate content and acetate to propionate ratio, but increased total volatile fatty acids (VFA) and acetate contents. Supplementing CCA decreased pH and acetate to propionate ratio, but increased total VFA, acetate and propionate contents. Rumen protease and carboxymethyl-cellulase activities and fungi, bacteria and Butyrivibrio fibrisolvens numbers increased for BI or CCA supply. In addition, protozoa increased for BI addition, and protease activity and Prevotella ruminicola increased for CCA supply. When CCA was supplemented, positive responses of R. albus and Ruminobacter amylophilus numbers to BI addition were enhanced. Blood glucose concentration was unchanged with BI supply, but increased for CCA supply. Blood nonesterified fatty acids and ß-hydroxybutyrate contents reduced with BI or CCA supply. Supplementation with BI or CCA increased blood BI or CA content. The results showed that supplementing BI or/and CCA improved lactation performance and nutrient digestion, and CCA supply did not enhance the lactation performance response to BI supply.

Unveiling the fructose metabolism system in Staphylococcus aureus: insights into the regulatory role of FruR and the FruRKT operon in bacterial fitness.

BACKGROUND: The utilization of fructose as a carbon source and energy provider plays a crucial role in bacterial metabolism. Additionally, fructose metabolism directly impacts the pathogenicity and virulence of certain pathogenic microorganisms. RESULTS: In this study, we report the discovery of a fructose phosphotransferase system (PTS) in S. aureus. This system comprises three genes, namely fruR, fruK, and fruT, which are co-located in an operon that is indispensable for fructose utilization in S. aureus. Our findings confirm that these three genes are transcribed from a single promoter located upstream of the fruRKT operon. The fruR gene encodes a DeoR-type transcriptional regulator, designated as FruR, which represses the expression of the fruRKT operon by direct binding to its promoter region. Significantly, our experimental data demonstrate that the fruRKT operon can be induced by fructose, suggesting a potential regulatory mechanism involving intracellular fructose-1-phosphate as a direct inducer. Furthermore, we conducted RNA-seq analysis to investigate the specificity of FruR regulation in S. aureus, revealing that the fruRKT operon is predominantly regulated by FruR. CONCLUSIONS: In summary, this study has uncovered a fructose phosphotransferase system (PTS) in S. aureus, highlighting the essential role of the fruR, fruK, and fruT genes in fructose utilization. We confirmed their co-location within an operon and established FruR as a key regulator by binding to the operon's promoter. Importantly, we demonstrated that fructose can induce this operon, possibly through intracellular fructose-1-phosphate. Our identification of this PTS system represents the initial characterization of a fructose metabolism system in S. aureus.

Defining the biogeographical map and potential bacterial translocation of microbiome in human 'surface organs'.

The microbiome in a specific human organ has been well-studied, but few reports have investigated the multi-organ microbiome as a whole. Here, we aim to analyse the intra-individual inter-organ and intra-organ microbiome in deceased humans. We collected 1608 samples from 53 sites of 7 surface organs (oral cavity, esophagus, stomach, small intestine, appendix, large intestine and skin; n = 33 subjects) and performed microbiome profiling, including 16S full-length sequencing. Microbial diversity varied dramatically among organs, and core microbial species co-existed in different intra-individual organs. We deciphered microbial changes across distinct intra-organ sites, and identified signature microbes, their functional traits, and interactions specific to each site. We revealed significant microbial heterogeneity between paired mucosa-lumen samples of stomach, small intestine, and large intestine. Finally, we established the landscape of inter-organ relationships of microbes along the digestive tract. Therefore, we generate a catalogue of bacterial composition, diversity, interaction, functional traits, and bacterial translocation in human at inter-organ and intra-organ levels.

Chromosome-level genome provides insight into the evolution and conservation of the threatened goral (Naemorhedus goral).

BACKGROUND: Gorals Naemorhedus resemble both goats and antelopes, which prompts much debate about the intragenus species delimitation and phylogenetic status of the genus Naemorhedus within the subfamily Caprinae. Their evolution is believed to be linked to the uplift of the Qinghai-Tibet Plateau (QTP). To better understand its phylogenetics, the genetic information is worth being resolved. RESULTS: Based on a sample from the eastern margin of QTP, we constructed the first reference genome for Himalayan goral Naemorhedus goral, using PacBio long-read sequencing and Hi-C technology. The 2.59 Gb assembled genome had a contig N50 of 3.70 Mb and scaffold N50 of 106.66 Mb, which anchored onto 28 pseudo chromosomes. A total of 20,145 protein-coding genes were predicted in the assembled genome, of which 99.93% were functionally annotated. Phylogenetically, the goral was closely related to muskox on the mitochondrial genome level and nested into the takin-muskox clade on the genome tree, rather than other so-called goat-antelopes. The cladogenetic event among muskox, takin and goral occurred sequentially during the late Miocene (~ 11 - 5 Mya), when the QTP experienced a third dramatic uplift with consequent profound changes in climate and environment. Several chromosome fusions and translocations were observed between goral and takin/muskox. The expanded gene families in the goral genome were mainly related to the metabolism of drugs and diseases, so as the positive selected genes. The Ne of goral continued to decrease since ~ 1 Mya during the Pleistocene with active glaciations. CONCLUSION: The high-quality goral genome provides insights into the evolution and valuable information for the conservation of this threatened group.