Study on the alleviative effect of Lactobacillus plantarum on Eimeria falciformis infection.

Coccidia of the genus Eimeria are specialized intracellular parasitic protozoa that cause severe coccidiosis when they infect their hosts. Animals infected with Eimeria develop clinical symptoms, such as anorexia, diarrhea, and hematochezia, which can even cause death. Although the current preferred regimen for the treatment of coccidiosis is antibiotics, this treatment strategy is limited by the ban on antibiotics and the growing problem of drug resistance. Therefore, the exploration of alternative methods for controlling coccidiosis has attracted much attention. Lactobacillus plantarum has been shown to have many beneficial effects. In this study, L. plantarum M2 was used as a research object to investigate the effect of L. plantarum on intestinal inflammation induced by infection with Eimeria falciformis in mice by detecting indicators, such as oocyst output, serum cytokines, and the intestinal microbiota. Compared with that in the infection group, the percent weight loss of the mice that were administered with L. plantarum M2 was significantly reduced (P < 0.05). Supplemented L. plantarum M2 and probiotics combined with diclazuril can reduce the total oocyst output significantly (P < 0.05, P < 0.001). L. plantarum M2 had outstanding performance in maintaining intestinal barrier function, and the levels of the mucin MUC1 and the tight junction protein E-cadherin were significantly elevated (P < 0.01, P < 0.05). Studies have shown that probiotic supplementation can alleviate adverse reactions after infection and significantly improve intestinal barrier function. In addition, probiotics combined with diclazuril could optimize the partial efficacy of diclazuril, which not only enhanced the effect of antibiotics but also alleviated their adverse effects. This study expands the application of probiotics, provides new ideas for alternative strategies for coccidia control, and suggests a basis for related research on lactobacilli antagonizing intracellular pathogen infection.IMPORTANCECoccidia of the genus Eimeria are specialized intracellular parasitic protozoa, and the current preferred regimen for the treatment of coccidiosis is antibiotics. However, due to antibiotic bans and drug resistance, the exploration of alternative methods for controlling coccidiosis has attracted much attention. In this work, we focused on Lactobacillus plantarum M2 and found that probiotic supplementation can alleviate adverse reactions after infection and improve intestinal barrier function. This study proposes the possibility of using lactic acid bacteria to control coccidiosis, and its potential mechanism needs further exploration.

YY1 mediated DCUN1D5 transcriptional activation promotes triple-negative breast cancer progression by targeting FN1/PI3K/AKT pathway.

Triple-negative breast cancer (TNBC) is more aggressive and has a higher metastasis rate compared with other subtypes of breast cancer. Due to the lack of drug-targetable receptors, chemotherapy is now the only available systemic treatment for TNBC. However, some patients might still develop drug resistance and have poor prognosis. Therefore, novel molecular biomarkers and new treatment targets are urgently needed for patients with TNBC. To provide molecular insights into TNBC progression, we investigated the function and the underlying mechanism of Defective in cullin neddylation 1 domain containing 5 (DCUN1D5) in the regulation of TNBC. By TCGA dataset and surgical specimens with immunohistochemical (IHC) staining method, DCUN1D5 was identified to be significantly upregulated in TNBC tumor tissues and negatively associated with prognosis. A series of in vitro and in vivo experiments were performed to confirm the oncogenic role of DCUN1D5 in TNBC. Overexpression of FN1 or PI3K/AKT activator IGF-1 could restore the proliferative and invasive ability induced by DCUN1D5 knockdown and DCUN1D5 could act as a novel transcriptional target of transcription factor Yin Yang 1 (YY1). In conclusion, YY1-enhanced DCUN1D5 expression could promote TNBC progression by FN1/PI3K/AKT pathway and DCUN1D5 might be a potential prognostic biomarker and therapeutic target for TNBC treatment.

Additional prognostic value of polymorphisms within the 3'-untranslated region of programmed cell death pathway genes in early-stage breast cancer.

Introduction: The programmed cell death (PCD) pathway plays an important role in restricting cancer cell survival and proliferation. However, limited studies have investigated the association between genetic variants in the 3'-untranslated region of the PCD pathway genes and breast cancer outcomes. Methods: In this study, we genotyped 28 potentially functional single nucleotide polymorphisms (SNPs) in 23 PCD pathway genes in 1,177 patients with early-stage breast cancer (EBC) from a Han Chinese population. The median follow-up period was 174 months. Results: Among all the candidate SNPs, four independent SNPs (rs4900321 and rs7150025 in ATG2B, rs6753785 in BCL2L11, and rs2213181 in c-Kit) were associated with invasive disease-free survival (iDFS), distant disease-free survival (DDFS), breast cancer-specific survival (BCSS) and overall survival (OS), respectively. Further combined genotypes of these four SNPs revealed that the survival decreased as the number of unfavorable genotypes increased (Ptrend = 1.0 × 10-6, 8.5 × 10-8, 3.6 × 10-4, and 1.3 × 10-4 for iDFS, DDFS, BCSS, and OS, respectively). Receiver operating characteristic curve analysis demonstrated that incorporating unfavorable genotypes and clinicopathological variables improved the ability to predict EBC survival (P = 0.006, 0.004, 0.029, and 0.019 for iDFS, DDFS, BCSS, and OS, respectively). Additionally, rs6753785 and rs2213181 were associated with BCL2L11 and c-Kit mRNA expression, respectively. Conclusions: Our results suggest that these four SNPs may act as novel biomarkers for EBC survival, possibly by modulating the expression of the corresponding genes.

Spleen tyrosine kinase inhibitor R406 has both antiviral and anti-inflammatory effects on severe influenza A infection.

Death due to severe influenza is usually a fatal complication of a dysregulated immune response more than the acute virulence of an infectious agent. Although spleen tyrosine kinase (SYK) as a critical immune signaling molecule and therapeutic target plays roles in airway inflammation and acute lung injury, the role of SYK in influenza virus infection is not clear. Here, we investigated the antiviral and anti-inflammatory effects of SYK inhibitor R406 on influenza infection through a coculture model of human alveolar epithelial (A549) and macrophage (THP-1) cell lines and mouse model. The results showed that R406 treatment increased the viability of A549 and decreased the pathogenicity and mortality of lethal influenza virus in mice with influenza A infection, decreased levels of intracellular signaling molecules under the condition of inflammation during influenza virus infection. Combination therapy with oseltamivir further ameliorated histopathological damage in the lungs of mice and further delayed the initial time to death compared with R406 treatment alone. This study demonstrated that phosphorylation of SYK is involved in the pathogenesis of influenza, and R406 has antiviral and anti-inflammatory effects on the treatment of the disease, which may be realized through multiple pathways, including the already reported SYK/STAT/IFNs-mediated antiviral pathway, as well as TNF-α/SYK- and SYK/Akt-based immunomodulation pathway.

Machine learning-based pathomics signature of histology slides as a novel prognostic indicator in primary central nervous system lymphoma.

PURPOSE: To develop and validate a pathomics signature for predicting the outcomes of Primary Central Nervous System Lymphoma (PCNSL). METHODS: In this study, 132 whole-slide images (WSIs) of 114 patients with PCNSL were enrolled. Quantitative features of hematoxylin and eosin (H&E) stained slides were extracted using CellProfiler. A pathomics signature was established and validated. Cox regression analysis, receiver operating characteristic (ROC) curves, Calibration, decision curve analysis (DCA), and net reclassification improvement (NRI) were performed to assess the significance and performance. RESULTS: In total, 802 features were extracted using a fully automated pipeline. Six machine-learning classifiers demonstrated high accuracy in distinguishing malignant neoplasms. The pathomics signature remained a significant factor of overall survival (OS) and progression-free survival (PFS) in the training cohort (OS: HR 7.423, p < 0.001; PFS: HR 2.143, p = 0.022) and independent validation cohort (OS: HR 4.204, p = 0.017; PFS: HR 3.243, p = 0.005). A significantly lower response rate to initial treatment was found in high Path-score group (19/35, 54.29%) as compared to patients in the low Path-score group (16/70, 22.86%; p < 0.001). The DCA and NRI analyses confirmed that the nomogram showed incremental performance compared with existing models. The ROC curve demonstrated a relatively sensitive and specific profile for the nomogram (1-, 2-, and 3-year AUC = 0.862, 0.932, and 0.927, respectively). CONCLUSION: As a novel, non-invasive, and convenient approach, the newly developed pathomics signature is a powerful predictor of OS and PFS in PCNSL and might be a potential predictive indicator for therapeutic response.

The critical role of RAGE in severe influenza infection: A target for control of inflammatory response in the disease.

Controlling the excessive inflammatory response is one of the key ways to reduce the severity and mortality of severe influenza virus infections. RAGE is involved in inflammatory responses and acute lung injuries. Here, we investigated the role of RAGE and its potential application as a target for severe influenza treatment through serological correlation analysis for influenza patients, and treatment with the RAGE inhibitor FPS-ZM1 on A549 cells or mice with influenza A (H1N1) infection. The results showed high levels of RAGE were correlated with immunopathological injury and severity of influenza, and FPS-ZM1 treatment increased the viability of A549 cells with influenza A infection and decreased morbidity and mortality of influenza A virus infection in mice. The RAGE/NF-κb inflammatory signaling pathway is a major targeting pathway for FPS-ZM1 treatment in severe influenza. These findings provide further insights into the immune injury of severe influenza and a potential targeting candidate for the disease treatment.

Exploration of the relationship between tumor-infiltrating lymphocyte score and histological grade in breast cancer.

BACKGROUND: The histological grade is an important factor in the prognosis of invasive breast cancer and is vital to accurately identify the histological grade and reclassify of Grade2 status in breast cancer patients. METHODS: In this study, data were collected from 556 invasive breast cancer patients, and then randomly divided into training cohort (n = 335) and validation cohort (n = 221). All patients were divided into actual low risk group (Grade1) and high risk group (Grade2/3) based on traditional histological grade, and tumor-infiltrating lymphocyte score (TILs-score) obtained from multiphoton images, and the TILs assessment method proposed by International Immuno-Oncology Biomarker Working Group (TILs-WG) were also used to differentiate between high risk group and low risk group of histological grade in patients with invasive breast cancer. Furthermore, TILs-score was used to reclassify Grade2 (G2) into G2 /Low risk and G2/High risk. The coefficients for each TILs in the training cohort were retrieved using ridge regression and TILs-score was created based on the coefficients of the three kinds of TILs. RESULTS: Statistical analysis shows that TILs-score is significantly correlated with histological grade, and is an independent predictor of histological grade (odds ratio [OR], 2.548; 95%CI, 1.648-3.941; P < 0.0001), but TILs-WG is not an independent predictive factor for grade (P > 0.05 in the univariate analysis). Moreover, the risk of G2/High risk group is higher than that of G2/Low risk group, and the survival rate of patients with G2/Low risk is similar to that of Grade1, while the survival rate of patients with G2/High risk is even worse than that of patients with G3. CONCLUSION: Our results suggest that TILs-score can be used to predict the histological grade of breast cancer and potentially to guide the therapeutic management of breast cancer patients.

Epidemiological investigation of Cryptosporidium in children with diarrhea in middle Inner Mongolia, China.

Cryptosporidia (Cryptosporidium) is a protozoan that is widely parasitic in the intestinal cells of humans and animals, and it is also an important zoonotic parasite. However, there is no epidemiological investigation on Cryptosporidium spp. infection in infants with diarrhea of Inner Mongolia, the largest livestock region in China. To investigate the prevalence of Cryptosporidium, 2435 fresh fecal samples were collected from children with diarrhea in Inner Mongolia Maternal and Child Health Care Hospital. Molecular characterization of Cryptosporidium was carried out based on its 18S rRNA and gp60 gene sequences. The overall prevalence was 12.85% (313/2435), and in Hohhot (12.15%), it was lower than that in the surrounding city (14.87%) (P < 0.05). Moreover, Cryptosporidium was detected in different seasons and sexes. Concerning the age of children with diarrhea, the prevalence of those age groups between 0 and 1 was obviously lower than others, and there were significant differences in the prevalence at different ages (P < 0.001). Analysis of the 18S rRNA gene sequence revealed that all the positive samples were Cryptosporidium parvum, and there were 5 subtypes (IIdA23G3, IIdA24G3, IIdA24G4, IIdA25G3, and IIdA25G4). To the best of our knowledge, the above subtypes have not been reported. Our results provide a relevant basis for control and education on food safety and foodborne illness prevention.

Influence of Annealing Process on Soft Magnetic Properties of Fe-B-C-Si-P Amorphous Alloys.

It is well known that the annealing process plays a key role in tuning the properties of Fe-based amorphous soft magnetic alloys. However, the optimal annealing process for a particular amorphous alloy is often difficult to determine. Here, Fe81.4B13.2C2.8Si1.8P0.8 and Fe82.2B12.4C2.8Si1.8P0.8 amorphous alloys (denoted as Fe81.4 and Fe82.2) were prepared to systematically study the effects of the annealing temperature and time on the soft magnetic properties. The results show that the optimum annealing temperature ranges of the Fe81.4 and Fe82.2 amorphous alloys were 623 K to 653 K and 593 K to 623 K, and their coercivity (Hc) values were only 2.0-2.5 A/m and 1.3-2.7 A/m, respectively. Furthermore, a characteristic temperature Tai was obtained to guide the choosing of the annealing temperature at which the dBs/dT begins to decrease rapidly. Based on the theory of spontaneous magnetization, the relationship between Tai and the optimum annealing temperature ranges was analyzed. When the annealing temperature was higher than Tai, the effect of the internal magnetic field generated by spontaneous magnetization on the relaxation behavior was significantly reduced, and the alloys exhibited excellent soft magnetic properties. It is worth indicating that when annealed at 603 K (slightly higher than Tai), the Fe82.2 amorphous alloys exhibited excellent and stable soft magnetic properties even if annealed for a long time. The Hc of Fe82.2B12.4C2.8Si1.8P0.8 amorphous alloys was only 1.9 A/m when annealed at 603 K for 330 min. This value of Tai is expected to provide a suggestion for the proper annealing temperature of other amorphous soft magnetic alloys.

Characteristics of Immunocytes and Cytokines in Patients with Bloodstream Infections Caused by Carbapenem-Resistant Klebsiella pneumoniae in China.

Objective: To evaluate the characteristics of immunocytes and cytokines associated with bloodstream infections (BSIs) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Methods: Patients with BSIs K. pneumoniae (BSIs-Kpn) were enrolled in our hospital between 2015 and 2022. Whole blood and serum samples were collected on the first day after diagnosis. Immunocytes and cytokines profiles were assessed using multicolor flow cytometry and multiplex immunoassays, respectively. The test cytokines included interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-2, IL-4, IL-6, IL-10, and IL-17A. Results: A total of 313 patients had BSIs-Kpn, including 145 with CRKP, 43 with extended-spectrum ß-lactamases (ESBL) producing Kpn (ESBL-Kpn) and 125 with non-CRKP or non-ESBL-Kpn (susceptible Kpn, S-Kpn). Absolute number of leukomonocyte (CD45+) in CRKP, ESBL-Kpn and S-Kpn were 280.0 (138.0-523.0) cells/µL, 354.5 (150.3-737.3) cells/µL, and 637.0 (245.0-996.5) cells/µL, respectively. Compared with S-Kpn group, the absolute numbers of leukomonocyte (including T lymphocytes, B lymphocytes and natural killer cells) in patients with CRKP were significantly lower than that in patients with S-Kpn (P < 0.01). The levels of cytokines IL-2 and IL-17A were significantly higher in patients with S-Kpn than in those patients with CRKP (P<0.05). The area under receiver operating curve (AUC) of IL-2, IL-4, and IL-17A for S-Kpn was 0.576, 0.513, and 0.561, respectively, whereas that for the combination of these three cytokines with immunocytes was 0.804. Conclusion: Patients with BSIs-CRKP had lower leukomonocyte counts. High levels of IL-2 and IL-17A combined with immunocyte subpopulations showed relatively high diagnostic value for BSIs-S-Kpn from BSIs-CRKP.

Proper doses of brassinolide enhance somatic embryogenesis in different competent Korean pine cell lines during embryogenic callus differentiation.

Somatic embryogenesis of Korean pine (Pinus koraiensis Sieb. Et Zucc.), an ecologically and econimically very important conifer species, was hindered by the gradually weakens and fast runaway of the embryogenicity and embryo competence of the embryogenic callus. Brassinolide (BL) has shown the enhancing capability of somatic embryo regeneration. For checking the function of BL in this issue, we applied different concentrations of BL to Korean pine callus materials exhibiting different embryogenic capacities and subsequently monitored the physiological alterations and hormone dynamics of the embryogenic callus. Our study revealed that calli with different embryogenic strengths responded differently to different concentrations of BL, but the effect after the addition of BL was very uniform. The addition of BL during the proliferation phase of embryogenic callus may help to stimulate the biological activity of callus during the proliferation process and improve the level of cell metabolism, which is accompanied by a reduction in storage substances. BL could reduce the level of endogenous auxin IAA in embryogenic callus and increase the level of abscisic acid to regulate cell division and differentiation. In addition, the MDA content in the callus was significantly decreased and the activity of antioxidant enzymes was significantly increased after the addition of BL. During the proliferation of embryogenic callus, BL was added to participate in the metabolism of phenylpropane in the cells and to increase the activity of phenylalanine ammonia-lyase and the content of lignin in the cells. We deduced that the proper doses of BL for Korean pine embryogenic callus culture were as follow: calli with low, high and decreasing embryogenicity were subcultured after the addition of 0.75 mg/L, 0.35 mg/L, 2.00 mg/L BL, respectively, during proliferation culture stage.

LOX-1 regulation of H-type vascular endothelial cell regeneration in hyperglycemia.

AIMS: Diabetic osteoporosis (DOP) is the most common secondary form of osteoporosis. Diabetes mellitus affects bone metabolism; however, the underlying pathophysiological mechanisms remain unclear. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) expression is upregulated in conditions characterized by vascular injury, such as atherosclerosis, hypertension, and diabetes. Additionally, Notch, HIF-1α, and VEGF are involved in angiogenesis and bone formation. Therefore, we aimed to investigate the expression of Notch, HIF-1α, and VEGF in the LOX-1 silencing state. METHODS: Rat bone H-type vascular endothelial cells (THVECs) were isolated and cultured in vitro. Cell identification was performed using immunofluorescent co-expression of CD31 and Emcn. Lentiviral silencing vector (LV-LOX-1) targeting LOX-1 was constructed using genetic recombination technology and transfected into the cells. The experimental groups included the following: NC group, HG group, LV-LOX-1 group, LV-CON group, HG + LV-LOX-1 group, HG + LV-CON group, HG + LV-LOX-1 + FLI-06 group, HG + LV-CON + FLI-06 group, HG + LV-LOX-1 + LW6 group, and HG + LV-CON + LW6 group. The levels of LOX-1, Notch, Hif-1α, and VEGF were detected using PCR and WB techniques to investigate whether the expression of LOX-1 under high glucose conditions has a regulatory effect on downstream molecules at the gene and protein levels, as well as the specific molecular mechanisms involved. RESULTS: High glucose (HG) conditions led to a significant increase in LOX-1 expression, leading to inhibition of angiogenesis, whereas silencing LOX-1 can reverse this phenomenon. Further analysis reveals that changes in LOX-1 will promote changes in Notch/HIF-1α and VEGF. Moreover, Notch mediates the activation of HIF-1α and VEGF. CONCLUSIONS: The activation of LOX-1 and the inhibition of Notch/HIF-1α/VEGF in THVECs are the main causes of DOP. These findings contribute to our understanding of the pathogenesis of DOP and offer a novel approach for preventing and treating osteoporosis.

Assessing the impact of pine wilt disease on aboveground carbon storage in planted Pinus massoniana Lamb. forests via remote sensing.

The continuous spread of Bursaphelenchus xylophilus (Steiner and Buhrer) Nickle, commonly known as the organism that causes pine wilt disease (PWD), has become a notable threat to forest security in East Asia and southern Europe, and an assessment of the carbon loss caused by PWD damage is important to achieving carbon neutrality. This study used satellite remote sensing and 15-year ground monitoring data to measure the impact of PWD on the carbon storage of Pinus massoniana Lamb. (P. massoniana), the conifer with the largest planted area in southern China. This study showed that the occurrence of PWD had an impact on the increase in carbon storage of P. massoniana. The infected and dead P. massoniana trees accounted for only 1.46 % of the total number of trees but caused a carbon storage loss of 1.99 t/ha, which accounted for 6.23 % of the total carbon sink in healthy P. massoniana forests over the last 15 years. The most pronounced decline in carbon storage occurred in the first five years of PWD invasion. After 10 years of clearcutting and replanting of Schima superba Gardn. et Champ., the increase in carbon storage of the reformed forest far exceeded that of the healthy forest during the same period, which was 2.04 times (10 years) and 1.56 times (15 years) that of the healthy P. massoniana forest. In addition, our study found that during the 15-year period (from the forest age of 22 to the forest age of 37), the average carbon storage of P. massoniana forest was 31.9 t/ha. This study helps to evaluate the impact of PWD on the carbon sink of pine forests and provides methodological references for analyzing the impact of biological disturbances on the carbon cycle.

Comparison of effectiveness and cost of different HCV testing strategies in high-risk populations in China.

High-risk populations are the predominant populations affected by hepatitis C virus (HCV) infection, and there is an urgent need for efficient and cost-effective HCV testing strategies for high-risk populations to identify potential undiagnosed HCV-infected individuals. This study compared several commonly used testing strategies and conducted effectiveness and cost analysis to select the appropriate testing strategy for diagnosing HCV infection in high-risk populations. Among the 2093 samples from high-risk populations in this study, 1716 were HCV negative, 237 were current HCV infection, 137 were past HCV infection, and three were acute early HCV infection. It was found that out of 237 patients with HCV current infection, Strategy A could detect 225 cases, with a missed detection rate of 5.06%, and the total cost was 33 299 RMB. In addition, Strategy B could detect 237 cases of current HCV infection, and the HCV missed detection rate was 0.00%, and the total cost was 147 221 RMB. While 137 cases of past HCV infection could be distinguished by strategy C, but 14 cases with current HCV infection were missed, with an HCV-positive missed detection rate of 5.91%, and the total cost for Strategy C was 43 059 RMB. In conclusion, in high-risk populations, the HCV positivity rate is typically higher. If feasible, the preferred approach is to directly conduct HCV RNA testing, which effectively minimizes the risk of missing cases. However, in situations with limited resources, it is advisable to initially choose a highly sensitive method for anti-HCV screening, followed by HCV RNA testing on reactive samples.

Prognostic significance of collagen signatures at breast tumor boundary obtained by combining multiphoton imaging and imaging analysis.

PURPOSE: Collagen features in breast tumor microenvironment is closely associated with the prognosis of patients. We aim to explore the prognostic significance of collagen features at breast tumor border by combining multiphoton imaging and imaging analysis. METHODS: We used multiphoton microscopy (MPM) to label-freely image human breast tumor samples and then constructed an automatic classification model based on deep learning to identify collagen signatures from multiphoton images. We recognized three kinds of collagen signatures at tumor boundary (CSTB I-III) in a small-scale, and furthermore obtained a CSTB score for each patient based on the combined CSTB I-III by using the ridge regression analysis. The prognostic performance of CSTB score is assessed by the area under the receiver operating characteristic curve (AUC), Cox proportional hazard regression analysis, as well as Kaplan-Meier survival analysis. RESULTS: As an independent prognostic factor, statistical results reveal that the prognostic performance of CSTB score is better than that of the clinical model combining three independent prognostic indicators, molecular subtype, tumor size, and lymph nodal metastasis (AUC, Training dataset: 0.773 vs. 0.749; External validation: 0.753 vs. 0.724; HR, Training dataset: 4.18 vs. 3.92; External validation: 4.98 vs. 4.16), and as an auxiliary indicator, it can greatly improve the accuracy of prognostic prediction. And furthermore, a nomogram combining the CSTB score with the clinical model is established for prognosis prediction and clinical decision making. CONCLUSION: This standardized and automated imaging prognosticator may convince pathologists to adopt it as a prognostic factor, thereby customizing more effective treatment plans for patients.

Mettl3-dependent m6A modification is essential for effector differentiation and memory formation of CD8+ T cells.

Efficient immune responses rely on the proper differentiation of CD8+ T cells into effector and memory cells. Here, we show a critical requirement of N6-Methyladenosine (m6A) methyltransferase Mettl3 during CD8+ T cell responses upon acute viral infection. Conditional deletion of Mettl3 in CD8+ T cells impairs effector expansion and terminal differentiation in an m6A-dependent manner, subsequently affecting memory formation and the secondary response of CD8+ T cells. Our combined RNA-seq and m6A-miCLIP-seq analyses reveal that Mettl3 deficiency broadly impacts the expression of cell cycle and transcriptional regulators. Remarkably, Mettl3 binds to the Tbx21 transcript and stabilizes it, promoting effector differentiation of CD8+ T cells. Moreover, ectopic expression of T-bet partially restores the defects in CD8+ T cell differentiation in the absence of Mettl3. Thus, our study highlights the role of Mettl3 in regulating multiple target genes in an m6A-dependent manner and underscores the importance of m6A modification during CD8+ T cell response.

Prognostic Value of Immunohistochemistry-based Subtyping Before and After Neoadjuvant Chemotherapy in Patients with Triple-negative Breast Cancer.

To assess the predictive and prognostic value of a subtyping method based on immunohistochemistry in patients with triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC). This study included patients with TNBC treated with anthracycline- and taxane-based NAC and curative surgery. Immunohistochemical (IHC) subtyping was performed using core needle biopsy specimens before NAC (pre-NAC) and residual tumors after NAC (post-NAC). Logistic regression was performed to identify predictive biomarkers of pathological complete response (pCR). Invasive disease-free survival (iDFS), distant disease-free survival (DDFS), and overall survival (OS) were assessed using the log-rank test and Cox proportional hazards regression. A total of 230 patients were followed up for a median of 59 months. Clinical lymph node status and the pre-NAC subtype were independent predictors of pCR (P=0.006 and 0.005, respectively). The pre-NAC subtype was an independent prognostic factor for long-term survival (iDFS: P < 0.001, DDFS: P=0.010, and OS: P=0.044). Among patients with residual disease (RD) after NAC, approximately 45% of tumors changed their IHC subtype. Furthermore, the post-NAC subtype, but not the pre-NAC subtype, was strongly associated with the survival of patients with RD (iDFS: P < 0.001, DDFS: P=0.005, and OS: P=0.006). The IHC subtype predicted response to NAC and long-term survival in patients with early TNBC. In patients with RD, almost 45% of the tumors changed subtype after NAC. The IHC subtype should be considered when planning additional therapies pre- and post-NAC.

Electrospun VO2/carbon fibers for aqueous zinc-ion batteries.

Aqueous zinc-ion batteries (AZIBs) have become one of the most potential energy storage devices due to their high safety and low cost. Vanadium oxide is an ideal cathode material for AZIBs because of its unique tunnel structure and multivalent nature. In this work, electrospun VO2/carbon fibers (VO2@CPAN) with a three-dimensional (3D) network are obtained by an electrospinning strategy combining with a controlled heat treatment. As cathode for AZIBs, the 3D network of the carbon fiber significantly improves the conductivity of VO2, avoids the agglomeration of VO2, and increases the stability of VO2. Therefore, VO2@CPAN delivers a specific capacity of 323.2 mA h g-1 at 0.2 A g-1, which is higher than pure VO2. At the same time, excellent capacity retention of 76.6% is obtained at high current density of 10 A g-1 after 3000 cycles.

Electro-nape-acupuncture regulates the differentiation of microglia through PD-1/PD-L1 reducing secondary brain injury in acute phase intracerebral hemorrhage rats.

INTRODUCTION: This study aimed to investigate the effect of electro-nape-acupuncture (ENA) on the differentiation of microglia and the secondary brain injury in rats with acute-phase intracerebral hemorrhage (ICH) through the programmed cell death protein-1/ligand-1 (PD-1/PD-L1) pathway. METHODS: A total of 27 male Sprague-Dawley rats were randomly divided into three groups: sham group, ICH group, and ENA group. The autologous blood infusion intracerebral hemorrhage model was used to study the effects of ENA by administering electroacupuncture at GB20 (Fengchi) and Jiaji (EX-B2) acupoints on 24 h after the modeling, once per day for 3 days. The neurological function damage, hematoma lesion, and inflammatory cell infiltration were measured by the beam walking test and hematoxylin-eosin staining. The expression of PD-1, PD-L1, CD86, CD206, and related cytokines around the hematoma was measured by western blot, quantitative reverse transcription polymerase chain reaction, and immunofluorescence. RESULTS: The ICH group had significant neurological deficits (p < .001), hematoma lesions, and inflammatory cell infiltration. The levels of CD86 protein, inflammatory factors tumor necrosis factors (TNF)-α, interleukin (IL)-1ß, and IL-6 were increased (p < .001), while CD206 protein was reduced (p < .01), and the number of CD86+ /CD11b+ cells was also increased (p < .001) compared to the sham group. However, after ENA intervention, there was a significant reduction in neurological function damage (p < .05), infiltration of inflammatory cells, and the expression levels of CD86+ /CD11b+ cells (p < .05), resulting in the increased expression of PD-1 protein and differentiation of M2 phenotype significantly (p < .001). CONCLUSION: The study concludes that ENA could reduce neurological function damage, inhibit the expression of pro-inflammatory cytokines, and improve the infiltration of inflammatory cells to improve secondary brain injury in acute-phase intracerebral hemorrhage rats. These effects could be related to the increased expression of PD-1 around the lesion, promoting the differentiation of microglia from M1 to M2 phenotype.

Differences in Toxoplasma gondii distribution in different muscle and viscera of naturally infected sheep.

Toxoplasma gondii (T. gondii) is a zoonotic parasite that can cause serious pathology in intermediate hosts such as humans and animals. Eating undercooked or raw meat is the most important route of infection by T. gondii. Sheep are an important source of meat worldwide, and they are also susceptible to T. gondii. Mutton infected with T. gondii poses a serious threat to the food safety of consumers. At present, studies have mainly focused on the infection ratio of T. gondii in livestock; however, systematic studies have not been performed on differences in the distribution of this parasite in different muscle and viscera tissues of animals. In this study, the differences in the distribution of T. gondii in naturally infected Small-tailed Han sheep was studied. By amplifying the B1 gene of the parasite via real-time fluorescence quantification PCR (RT‒qPCR), we found that the parasite burden of T. gondii differed among different parts of the sheep, with the highest burden observed in the heart among the viscera and the external ridge among the muscle. The relative expression was ranked from high to low in our study as follows: heart, spleen, external ridge, tenderloin, lung, liver, kidney, neck meat, forelegs, cucumber strips, hind leg, lamb belly, and lamb chops. This study provided important guidance for monitoring the food safety of mutton products.