Neonatal IL-4 Over-Exposure is Accompanied by Macrophage Accumulation in Dura Mater After Instant Anti-inflammatory Cytokine Response in CSF.

Multiple studies have shown that clinical events resulting into neonatal IL-4 over-exposure, such as asthma in early life and food allergy, were associated with brain damage and that the neuroinflammation induced by them might lead to cognitive impairments, anxiety-/depressive-like behaviors. IL-4 is the most major elevated cytokine in periphery when these clinical events occur and peripheral IL-4 level positively correlates with the severity of those events. Our previous studies have verified that neonatal IL-4 over-exposure induced a delayed neuroinflammatory damage in rodents, which might have adverse implications for brain development and cognition. Neuroinflammation in brain parenchyma is often accompanied by changes in CSF cytokines levels. However, whether the cytokines levels in CSF change after neonatal IL-4 over-exposure is unknown. Here, we found a delayed pro-inflammatory cytokines response (higher IL-6, IL-1ß and, TNF levels) in both hippocampus and CSF after an instant anti-inflammatory cytokine response in IL-4 over-exposed rats. Moreover, the pro-inflammatory cytokines response appeared earlier in CSF than in hippocampus. The level of each of the pro-inflammatory cytokines in CSF positively correlated with that in hippocampus at the age of postnatal day 42. More microglia numbers/activation and higher M-CSF level in the hippocampus in IL-4 over-exposed rats were also observed. Furthermore, there were more macrophages with inflammatory activation in dural mater of IL-4 over-exposed rats. In sum, neonatal IL-4 over-exposure in rats induces delayed inflammation in CSF, suggesting CSF examination may serve as a potential method in predicting delayed neuroinflammation in brain following neonatal IL-4 over-exposure.

Analysis of minimal levator ani hiatus area based on MRI in female adults without pelvic floor dysfunction at different age groups.

PURPOSE: To investigate the association of minimal levator ani hiatus area with age in female adults without pelvic floor dysfunction. METHODS: 532 female subjects aged 18 ~ 90 years without pelvic floor dysfunction, divided into four groups (Group A, 18 ~ 29 years old; Group B, 30 ~ 39 years old; Group C, 40 ~ 49 years old; Group D, ≥ 50 years old) based on age, underwent traditional pelvic two-dimensional (2D) T2-weighted imaging (T2WI) axial to the body (AxB) for measuring the minimal levator ani hiatus area. 39 female volunteers were re-recruited to undergo both traditional pelvic 2D T2WI AxB and three-dimensional (3D) T2WI. An axial plane parallel to the direction of the puborectalis muscle (AxPRM) was acquired based on 3D T2WI. The difference of levator ani hiatus area measured on AxB and AxPRM images in 39 female volunteers was compared by one-sample t test, to verify if minimal levator ani hiatus area can be acquired on the traditional pelvic 2D T2WI AxB images. Spearman analysis evaluated the association of minimal levator ani hiatus area with age and the rank-sum test analyzed the area differences among four age groups. RESULTS: Female age was positively correlated with minimal levator ani hiatus area (r = 0.23; p < 0.001). The minimal levator ani hiatus areas of 532 subjects were: 15.17 ± 1.77 cm2 in Group A, 15.52 ± 2.21 cm2 in Group B, 16.03 ± 2.16 cm2 in Group C, and 16.40 ± 2.10 cm2 in Group D. ANOVA showed significant statistical differences among four age groups (F = 7.519, p < 0.0001). Significant differences in minimal levator ani hiatus areas were found between Group A and Group C (p = 0.0491), Group A and Group D (p = 0.0007), and Group B and Group D (p < 0.001). There was no statistical difference in minimal levator ani hiatus areas measured on AxB and AxPRM images in 39 female volunteers (p = 0.1000). There were no statistical difference in minimal levator ani hiatus areas between nulliparous and multiparous group for each age group (all p > 0.05). CONCLUSIONS: Based on a large sample, this study summarized the minimum levator ani hiatus area of female adults without pelvic floor dysfunction in different age groups. We found significant differences among different age groups. In addition, a positive correlation was found between age and the minimum levator ani hiatus area. These findings can provide reference criteria for diagnosing pelvic organ prolapse in female adults of different age groups.

Fusobacterium nucleatum induces excess methyltransferase-like 3-mediated microRNA-4717-3p maturation to promote colorectal cancer cell proliferation.

Fusobacterium nucleatum infection plays vital roles in colorectal cancer (CRC) progression. Overexpression of microRNA-4717-3p (miR-4717) was reported to be upregulated in F. nucleatum positive CRC tissues, however, the underlying mechanism is unknown. In this study, we found that miR-4717 promoted CRC cell proliferation in vitro and growth of CRC in vivo following F. nucleatum infection. MicroRNA-4717 suppressed the expression of mitogen-activated protein kinase kinase 4 (MAP2K4), a tumor suppressor, by directly targeting its 3'-UTR. Furthermore, we confirmed that methyltransferase-like 3 (METTL3)-dependent m6 A methylation could methylate primary (pri)-miR-4717, which further promoted the maturation of pri-miR-4717, and METTL3 positively regulated CRC cell proliferation through miR-4717/MAP2K4 pathways. In conclusion, F. nucleatum-induced miR-4717 excessive maturation through METTL3-dependent m6 A modification promotes CRC cell proliferation, which provides a potential therapeutic target and diagnostic biomarker for CRC.

Tauroursodeoxycholic acid prevents Burkholderia pseudomallei-induced endoplasmic reticulum stress and is protective during melioidosis in mice.

BACKGROUND: Burkholderia pseudomallei, a facultative intracellular bacterium, is the aetiological agent of melioidosis that is responsible for up to 40% sepsis-related mortality in epidemic areas. However, no effective vaccine is available currently, and the drug resistance is also a major problem in the treatment of melioidosis. Therefore, finding new clinical treatment strategies in melioidosis is extremely urgent. RESULTS: We demonstrated that tauroursodeoxycholic acid (TUDCA), a clinically available endoplasmic reticulum (ER) stress inhibitor, can promote B. pseudomallei clearance both in vivo and in vitro. In this study, we investigated the effects of TUDCA on the survival of melioidosis mice, and found that treatment with TUDCA significantly decreased intracellular survival of B. pseudomallei. Mechanistically, we found that B. pseudomallei induced apoptosis and activated IRE1 and PERK signaling ways of ER stress in RAW264.7 macrophages. TUDCA treatment could reduce B. pseudomallei-induced ER stress in vitro, and TUDCA is protective in vivo. CONCLUSION: Taken together, our study has demonstrated that B. pseudomallei infection results in ER stress-induced apoptosis, and TUDCA enhances the clearance of B. pseudomallei by inhibiting ER stress-induced apoptosis both in vivo and in vitro, suggesting that TUDCA could be used as a potentially alternative treatment for melioidosis.

Asia Pacific road transportation emissions, 1900-2050.

Asia Pacific (AP) is the largest regional vehicle market and accounted for 48% of global sales in 2019. Air quality is a pressing issue in many AP countries and together with increased vehicle sales has led to intense scrutiny of vehicle emissions. The heterogeneity of socio-economic features and transportation patterns in AP countries has resulted in different emission levels and control policies. We present an assessment of the historical and future emissions of on-road transportation and strategies to tackle emission challenges. First, we collected historical country-level population, economic development, vehicle ownership, and transportation policy data from 1900 to 2020, and forecast future development of on-road transportation activity (both passenger and freight) based on its historical relationship with socio-economic development through 2050. We considered major countries (China, India, Japan, South Korea, Australia) individually and other AP countries as a group. Second, we generated a series of emission control scenarios with various stringency levels after a comprehensive review of vehicle control measures implemented in AP countries. The control packages included transportation mode shifts, pollutant emission standards, fuel consumption standards, fuel and powertrain diversification, improvement in fuel quality, and economic and transportation policies. Localized emission factors for greenhouse gases (GHGs) and criteria air pollutants (carbon monoxide (CO), nitrogen oxides (NOx), and particulate matter (PM)) were collected and estimated in line with the emission control measures. Third, we estimated historical and future emissions of AP on-road transportation from 1900 to 2050. The results showed that major air pollutants (NOx, CO, and PM2.5) from on-road vehicles peaked in 2000-2010 and are now declining despite increasing vehicle population. Control of GHGs is more challenging than for criteria air pollutants. In our reference scenario where existing policies and emission standards are implemented and new technologies are adopted according to national plans, road transportation GHG emissions in AP peak in approximately 2040.

Life Cycle Greenhouse Gas Emissions for Last-Mile Parcel Delivery by Automated Vehicles and Robots.

Increased E-commerce and demand for contactless delivery during the COVID-19 pandemic have fueled interest in robotic package delivery. We evaluate life cycle greenhouse gas (GHG) emissions for automated suburban ground delivery systems consisting of a vehicle (last-mile) and a robot (final-50-feet). Small and large cargo vans (125 and 350 cubic feet; V125 and V350) with an internal combustion engine (ICEV) and battery electric (BEV) powertrains were assessed for three delivery scenarios: (i) conventional, human-driven vehicle with human delivery; (ii) partially automated, human-driven vehicle with robot delivery; and (iii) fully automated, connected automated vehicle (CAV) with robot delivery. The robot's contribution to life cycle GHG emissions is small (2-6%). Compared to the conventional scenario, full automation results in similar GHG emissions for the V350-ICEV but 10% higher for the V125-BEV. Conventional delivery with a V125-BEV provides the lowest GHG emissions, 167 g CO2e/package, while partially automated delivery with a V350-ICEV generates the most at 486 g CO2e/package. Fuel economy and delivery density are key parameters, and electrification of the vehicle and carbon intensity of the electricity have a large impact. CAV power requirements and efficiency benefits largely offset each other, and automation has a moderate impact on life cycle GHG emissions.

An improved quantitative real-time polymerase chain reaction technology for Helicobacter pylori detection in stomach tissue and its application value in clinical precision testing.

BACKGROUND: Helicobacter pylori (H. pylori) infection is a serious human health threat. The empiric H. pylori treatment paradigm guided by traditional testing technologies has led to antibiotic resistance. Here, we improved the qPCR method to provide technical support for precision H. pylori diagnosis and treatment. METHODS: Two pairs of primers and probes targeting the glmM gene were designed to detect H. pylori, and a multiplex qPCR method was established for virulence factor detection. Then, a rapid urease test (RUT), culturing and qPCR were performed on 141 specimens collected from Xinqiao Hospital of China in 2017 to evaluate the qPCR detection capability. Finally, the H. pylori infectious amount and virulence genes were detected by qPCR. RESULTS: 1. The improved qPCR method which used two pairs of primers had a higher detection rate (100%) and better accuracy (p = 0.000), compared with the qPCR using a pair of primers. It also had better consistency with the bacterial culture than with RUT (Kappa =0.440, p < 0.001). 2. The H. pylori infectious amount was significantly positively associated with gastritis in corpus (p = 0.003) and gastric erosion (p = 0.043). The H. pylori infectious amount in gastric precancerous patients was significantly lower than that in H. pylori-positive patients (p < 0.05), and the infectious H. pylori-vacA s1+ amount was significantly greater than that of H. pylori-vacA s1- (p < 0.05). 3. The vacA s1 frequency was significantly higher than that of vacA m1/cagA+/babA2+ in chronic superficial gastritis (p = 0.000), peptic ulcer (p = 0.037) and gastric erosion (p = 0.009). The H. pylori-vacA+/cagA+/babA2+ frequency showed a significant positive correlation (p < 0.05). CONCLUSIONS: The H. pylori infectious amount and presence of H. pylori virulence factors showed complex correlations with gastric disease occurrence and development. The improved qPCR with good detection performance can be used for quantitative H. pylori detection and testing for the virulence genes vacA s1, vacA m1, cagA and babA2 simultaneously. These findings will provide valuable information for disease diagnosis and treatment.

Diffusion kurtosis imaging in liver: a preliminary reproducibility study in healthy volunteers.

OBJECTIVES: To systematically test the reproducibility of DKI technique in normal liver and report a complete set of DKI measurement data. MATERIALS AND METHODS: Thirty-two healthy volunteers were examined with liver DKI twice on the GE 3.0 T MRI scanner and reviewed by three professional experts. DKI-derived parameters fractional anisotropy of kurtosis (FAk), mean diffusivity (Md), axial diffusivity (Da), radial diffusivity (Dr), mean kurtosis (Mk), axial kurtosis (Ka), and radial kurtosis (Kr) in eight segments divided by Couinaud octagonal method were collected. Inter-class correlation coefficient (ICC) was used to assess the agreement between three experts. For each expert, the reproducibility of twice scans was evaluated by Bland-Altman method. Multivariate analysis of variance was to explore the regional distribution characteristics of DKI-derived parameters, and showed with box-plot graph. RESULTS: Using ICC analysis, except for FAk (ICC 0.312, 0.307), other DKI metric values showed high reproducibility (0.716 < ICC < 0.907) between three experts for each of two DKI measurements. With Bland-Altman method, liver segment 5 (S5) showed the best reproducibility between two DKI measurement, and the reproducibility of segment 4 (S4) was the worst. The reproducibility of the right lobe was significantly higher than the left lobe. The values of diffusion metrics (Md, Da, and Dr) and kurtosis metrics (Mk, Ka, and Kr) existed significantly difference between the right and left hepatic lobes. CONCLUSION: DKI has shown excellent reproducibility in liver imaging. The range of values for multiple DKI parameters, derived from the normal liver, was reported, and may provide data reference for further clinical DKI applications. Additionally, DKI technique is a non-invasive method to reflect the perfusion or structural differences between the left and right hepatic lobes from the molecular level.

[Promoting tanshinone synthesis of Salvia miltiorrhiza root by a seed endophytic fungus, Phoma herbarum D603].

The interaction of endophytes and host plant is an effective mean to regulate the growth and secondary metabolism of medicinal plants. Here we want to elucidate the effects and mechanism of Phoma herbarum D603 on the root development and tanshinone synthesis in root of Salvia miltiorrhiza by endophyte-plant coculture system. The mycelium of P. herbarum D603 was colonized in the root tissue space, and formed a stable symbiotic relationship with host plant. The in vitro activities analysis showed that the concentration of IAA produced by D603 can reach(6.45±0.23) µg·mL~(-1), and this strain had some abilities of phosphorus solubilization and siderophore production activities. The coculture experiment showed that strain D603 can significantly promote the synthesis and accumulation of tanshinones in the root of S. miltiorrhiza, in which after 8 weeks of treatment with D603, the content of tanshinone Ⅱ_A in the roots reached up to(1.42±0.59) mg·g~(-1). By the qRT-PCR analysis results, we found that D603 could improve the expression levels of some key genes(DXR, DXS, GGPP, HMGR, CPS) of tanshinone biosynthesis pathway in host plant S. miltiorrhiza, but the promoting effect mainly occurred in the early stage of the interaction, and the enzyme activity level decreased in varying degrees of the later stage. In summary, seed-associated endophyte P. herbarum D603 can promote the growth and root development of S. miltiorrhiza by producing hormones, promoting nutrient absorption and siderophore production, and promote the synthesis and accumulation of tanshinones by regulating the expression level of key genes in the synthetic pathway in S. miltiorrhiza.

Economic and Climate Benefits of Electric Vehicles in China, the United States, and Germany.

Mass adoption of electric vehicles (EVs) is widely viewed as essential to address climate change and requires a compelling case for ownership worldwide. While the manufacturing costs and technical capabilities of EVs are similar across regions, customer needs and economic contexts vary widely. Assessments of the all-electric-range required to cover day-to-day driving demand, and the climate and economic benefits of EVs, need to account for differences in regional characteristics and individual travel patterns. To meet this need travel profiles for 1681 light-duty passenger vehicles in China, the U.S., and Germany were used to make the first consistent multiregional comparison of customer and greenhouse gas (GHG) emission benefits of EVs. We show that despite differences in fuel prices, driving patterns, and subsidies, the economic benefits/challenges of EVs are generally similar across regions. Individuals who are economically most likely to adopt EVs have GHG benefits that are substantially greater than for average drivers. Such "priority" EV customers have large (32%-63%) reductions in cradle-to-grave GHG emissions. It is shown that low battery costs (below approximately $100/kWh) and a portfolio of EV offerings are required for mass adoption of electric vehicles.

Interleukin-33 Predicts Poor Prognosis and Promotes Renal Cell Carcinoma Cell Growth Through its Receptor ST2 and the JNK Signaling Pathway.

BACKGROUND/AIMS: Renal cell carcinoma (RCC) is currently the ninth most common cancer in men. Interleukin (IL)-33 expression has previously been associated with a number of cancers; however, its biological role in RCC is poorly understood. In this study, we sought to elucidate the role of IL-33 in RCC. METHODS: Serum IL-33 levels were measured by ELISA. IL-33 expression in clinical RCC samples was examined by immunocytochemistry. The proliferation and apoptosis rate of RCC were determined by CCK8 and flow cytometry. Mcl1 and Bcl-2 expression were measured by quantitative real-time PCR and western blotting. JNK expression were measured by western blotting and flow cytometry. The in vivo role of IL-33 in RCC tumorigenesis was examined by animal models. RESULTS: We found that increased expression of IL-33 in RCC was associated with tumor-lymph node-metastasis (TNM) stage and inversely correlated with prognosis. IL-33 enhances RCC cell growth in vivo and stimulates RCC cell proliferation and prevents chemotherapy-induced tumor apoptosis in vitro. Furthermore, we demonstrated that IL-33 promotes RCC cell proliferation and chemotherapy resistance via its receptor ST2 and the JNK signaling activation in tumor cells. CONCLUSION: Our findings suggest that targeting IL-33/ST2 and JNK signaling may have potential value in the treatment of RCC.

Occurrence and molecular characterization of Cryptosporidium in dogs in Henan Province, China.

BACKGROUND: Cryptosporidiosis in dogs has been reported worldwide, involving both asymptomatic and diarrheic dogs. Large-scale surveys of Cryptosporidium infection in dogs have been performed in some countries using different diagnostic methods. But, few data are available on the infection rate and molecular characteristics of Cryptosporidium spp. in dogs in China. RESULT: In this study, 770 fecal samples from 66 locations in Henan Province were examined. The average Cryptosporidium infection rate was 3.8%, with dogs in kennels having the highest rate of 7.0% (χ² = 14.82, P < 0.01). The infection rate was 8.0% in dogs younger than 90 days, which was significantly higher than that in the other age groups (1.1-3.8%;χ² = 18.82, P < 0.01). No association was noted between the infection rate and the sex of the dogs. Twenty-nine Cryptosporidium-positive samples were amplified at the small subunit rRNA (SSU rRNA), 70-kDa heat shock protein (HSP70), and actin loci using PCR. Sequence analysis of these amplicons identified only Cryptosporidium canis, which showed 100% identity with the published sequences of the SSU rRNA, HSP70, and actin genes. CONCLUSIONS: Our results confirm that C. canis is popular in the dog population in China, considering the large number of dogs in China and the close contact between dogs and humans, the role of C. canis in the transmission of human cryptosporidiosis warrants attention.

A Model of Long-Term Ventricular Fibrillation in Isolated Rat Hearts.

Ventricular fibrillation (VF) is a fatal arrhythmia with a high incidence in cardiac patients, but VF arrest under perfusion is a neglected method of intraoperative arrest in the field of cardiac surgery. With recent advances in cardiac surgery, the demand for prolonged VF studies under perfusion has increased. However, the field lacks simple, reliable, and reproducible animal models of chronic ventricular fibrillation. This protocol induces long-term VF through alternating current (AC) electrical stimulation of the epicardium. Different conditions were used to induce VF, including continuous stimulation with a low or high voltage to induce long-term VF and stimulation for 5 min with a low or high voltage to induce spontaneous long-term VF. The success rates of the different conditions, as well as the rates of myocardial injury and recovery of cardiac function, were compared. The results showed that continuous low-voltage stimulation induced long-term VF and that 5 min of low-voltage stimulation induced spontaneous long-term VF with mild myocardial injury and a high rate of recovery of cardiac function. However, the low-voltage, continuously stimulated long-term VF model had a higher success rate. High-voltage stimulation provided a higher rate of VF induction but showed a low defibrillation success rate, poor recovery of cardiac function, and severe myocardial injury. On the basis of these results, continuous low-voltage epicardial AC stimulation is recommended for its high success rate, stability, reliability, reproducibility, low impact on cardiac function, and mild myocardial injury.

Oral exposure to an acceptable daily intake dose of aspartame induced a delayed proinflammatory cytokine response in the cerebrospinal fluid of rats.

This study aimed to investigate the effect of exposure to aspartame (ASP) at safe levels on proinflammatory cytokines in the cerebrospinal fluid (CSF) of rats. Sprague Dawley rats were sacrificed after 1, 2, 4 or 8 week(s) of continuous exposure to ASP (40 mg/kg body weight). Serum, CSF and brain tissue samples were prepared, and the levels of the IL-1ß, IL-6 and TNF-α were analyzed by ELISA. In serum, the levels of all three cytokines showed a two-phase alteration, a decrease followed by an increase in the ASP group. In the brain, their levels increased from the second or fourth week compared with the control group. In CSF, the levels of these cytokines showed a similar change to that in brain tissue, but the increase appeared at a later time point. For each cytokine, there was a significant positive correlation between its levels in serum, brain tissue and CSF. This is the first discovery that ASP exposure increased the levels of proinflammatory cytokines in CSF in rats, which emerged later than in blood and brain tissue. This study suggests the necessity of conducting related clinical studies to evaluate potential neuroinflammatory effects induced by chronic ASP exposure through CSF analysis.

Activated partial thromboplastin time as a potential biomarker for the diagnosis of tuberculous pleural effusion.

BACKGROUND: The aim of this study was to explore the difference in activated partial thromboplastin time (APTT) levels in patients with tuberculous and non-tuberculous pleural effusion (TPE and non-TPE) and its possible mechanism to provide a new direction for the diagnosis of pleural effusion (PE). METHODS: A total of 61 patients diagnosed with tuberculous pleurisy with pleural effusion at Shunde Hospital of Southern Medical University from July 2013 to September 2020 were selected as the observation group (tuberculosis group). Another 89 patients (45 with malignant pleural effusion (MPE) and 44 with parapneumonic pleural effusion (PPE) composed the control group. The adenosine deaminase (ADA) level in pleural fluid and plasma APTT level were measured in the two groups. RESULTS: The levels of APTT and ADA in the TPE group were significantly higher than the control group, and were 40.03 (37.00, 42.60) (s) and 55.00 (47.00, 69.25) (U/L) for TPE, 29.50 (25.45, 34.20) (s) and 11.90 (9.15, 19.05) (U/L) for malignant pleural effusion (MPE) and 31.35 (27.43, 35.76) (s) and 15.15 (7.40, 35.00) (U/L) for parapneumonic pleural effusion (PPE), respectively. CONCLUSIONS: The level of plasma APTT has certain significance in differentiating tuberculous pleural effusion from nontuberculous pleural effusion.

Serodiagnosis of Abdominal Abscess Caused by Burkholderia pseudomallei: Case Report and Literature Review.

Burkholderia pseudomallei, the causative agent of melioidosis can be responsible for a wide spectrum of clinical manifestations and heterogeneous prognoses, with a high mortality in the acute onset. We report a case of a deep abdominal abscess with sepsis secondary to melioidosis in a young farmer from a non-high-risk population. Emergency medical treatment was administered according to the detection of serum antibodies against Hcp1, the results of which provided etiological evidence of B. pseudomallei infection for the timely and properly antimicrobial therapy in the absence of direct evidence of melioidosis. To our knowledge, this is the first reported case of serodiagnosis of acute exacerbation of melioidosis in China.

One-pot RPA-Cas12a assay for instant and visual detection of Burkholderia pseudomallei.

Burkholderia pseudomallei is the causative agent of melioidosis, a potentially life-threatening infectious disease, and poses public health risks in endemic areas. Due to the high mortality, intrinsic antibiotic resistance, and atypical manifestations, establishing a rapid, accurate, and sensitive identification of B. pseudomallei enables earlier diagnosis, proper treatments, and better outcomes of melioidosis. Herein, we present a One-Pot CRISPR-integrated assay for Instant and Visual Detection (termed OPC-IVD) of B. pseudomallei. The integration of recombinase polymerase amplification and CRISPR-Cas12a recognition-activated trans-cleavage, achieved a true all-in-one single-tube reaction system, initiating the amplification and cleavage simultaneously, which realized a facile sample-to-answer assay. This approach could be performed with simplified DNA extraction and completed around 30 min by holding the reaction tube in the hand. The detection limit of our OPC-IVD was determined to be 2.19 copy/uL of plasmid DNA, 12.5 CFU/mL of B. pseudomallei, and 61.5 CFU/mL of bacteria in spiked blood samples, respectively. Furthermore, the introduction of internal amplification control effectively reduced the occurrence of false negatives, which was incorporated in the reaction system, and amplified simultaneously with the target and read by naked eyes. The assay exhibited 100% accuracy when evaluated in clinical isolates and samples. The streamlined workflow of our OPC-IVD of B. pseudomallei enables a field-deployable, instrument-free, and ultra-fast approach that can be utilized by non-expert personnel in the field of molecular diagnosis of melioidosis especially in under-resourced setting.

Blocking coprophagy increases the levels of inflammation and depression in healthy mice as well as mice receiving fecal microbiota transplantation from disease model mice donors.

Rodents have been extensively used as animal models in microbiome studies. However, all rodents have a habitual nature called coprophagy, a phenomenon that they self-reinoculate feces into their gastrointestinal tract. Recent studies have shown that blocking coprophagy can alter rodents' diversity of gut microbiota, metabolism, neurochemistry, and cognitive behavior. However, whether rodents' coprophagy behavior affects the levels of inflammation and depression is unclear. In order to address this problem, we first blocked coprophagy in healthy mice. It displayed an increase in the levels of depression, verified by depressive-like behaviors and mood-related indicators, and inflammation, verified by the increased levels of the pro-inflammatory cytokine, in coprophagy-blocked mice. Furthermore, we transplanted fecal microbiota from chronic restraint stress (CRS) depression model mice and lipopolysaccharide (LPS) inflammation model mice to healthy recipient mice, respectively. It showed that the disease-like phenotypes in the coprophagy-blocked group were worse than those in the coprophagy-unblocked group, including severer depressive symptoms and higher levels of pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α and IFN-γ) in serum, prefrontal cortex (PFC), and hippocampus (HIP). These findings showed that blocking coprophagy in mice not only increased the levels of inflammation and depression in healthy mice but also aggravated inflammation and depression induced by fecal microbiota from disease donors. The discovery may provide a vital reference for future research involving FMT in rodents.

Single-cell sequencing of immune cells after marathon and symptom-limited cardiopulmonary exercise.

Vigorous-intensity leisure-time physical activity, such as marathon, has become increasingly popular, but its effect on immune functions and health is poorly understood. Here, we performed scRNA-seq analysis of peripheral blood mononuclear cells (PBMCs) after a bout of symptom-limited cardiopulmonary exercise (CPX) test or marathon. Time-series single-cell analysis revealed the detailed series of landscapes of immune cells in response to short and long vigorous-intensity activities. Reduction of effective T cells was observed with the cell migration and motility pathways enriched in circulation following marathon. Baseline values of PBMCs abundance were reached around 1 h after CPX and 24 h following marathon, but longer time was required for expression recovery of cytotoxicity genes. The ratio of effector/naive T cells was found to change uniformly among the participants and could serve as a better indicator for exercise intensity than the CD4+/CD8+ T cell ratio. Moreover, we identified time-dependent monocyte state transitions after marathon.

MicroRNA-31 induced by Fusobacterium nucleatum infection promotes colorectal cancer tumorigenesis.

Persistent Fusobacterium nucleatum infection is associated with the development of human colorectal cancer (CRC) and promotes tumorigenicity, but the underlying mechanisms remain unclear. Here, we reported that F. nucleatum promoted the tumorigenicity of CRC, which was associated with F. nucleatum-induced microRNA-31 (miR-31) expression in CRC tissues and cells. F. nucleatum infection inhibited autophagic flux by miR-31 through inhibiting syntaxin-12 (STX12) and was associated with the increased intracellular survival of F. nucleatum. Overexpression of miR-31 in CRC cells promoted their tumorigenicity by targeting eukaryotic initiation factor 4F-binding protein 1/2 (eIF4EBP1/2), whereas miR-31 knockout mice were resistant to the formation of colorectal tumors. In conclusion, F. nucleatum, miR-31, and STX12 form a closed loop in the autophagy pathway, and continuous F. nucleatum-induced miR-31 expression promotes the tumorigenicity of CRC cells by targeting eIF4EBP1/2. These findings reveal miR-31 as a potential diagnostic biomarker and therapeutic target in CRC patients with F. nucleatum infection.