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Abstract Background The Fusarium head blight caused by Fusarium graminearum results in reduced crop yields and the potential for vomitoxin contamination, which poses a risk to both human and livestock health. The primary method of control relies on the application of chemical fungicides. Results The current study found that the tebuconazole sensitivity of 165 F. graminearum isolates collected from the Huang-Huai-Hai region of China between 2019 and 2023 ranged from 0.005 to 2.029 µg/mL, with an average EC50 value of 0.33 ± 0.03 µg/mL. The frequency distribution conformed to a unimodal curve around the mean, and therefore provides a useful reference for monitoring the emergence of tebuconazole resistance in field populations of F. graminearum. No cross-resistance was detected between tebuconazole and other unrelated fungicides such as flutriafol, propiconazole and fluazinam, but there was a clear negative cross-resistance with triazole fungicides including fludioxonil, epoxiconazole, hexaconazole, and metconazole. Analysis of five tebuconazole-resistant mutants produced under laboratory conditions indicated that although the mycelial growth of the mutants were significantly (p

CD7-targeted chimeric antigen receptor-T (CAR-T) cell therapy has shown great promise in the treatment of relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL). In this study, we reported a case of a 34-year-old male patient with T-ALL who finally developed multi-line drug resistance and refractoriness after multiple lines of high-intensity chemotherapy. After physician evaluation, this patient received allogeneic hematopoietic stem cell transplantation (allo-HSCT). Then, The patient remained in complete remission (CR) for four months before a relapse with 26.64% chimerism rate, so he was treated with allogeneic anti-CD7 CAR-T cells after chemotherapy reducing the tumor burden. The CAR-T product was a novel anti-CD7 CAR-T based on retroviral vectors (RV). After infusion, the patient achieved CR within 1 month after anti-CD7 CAR-T infusion and the remission has been ongoing for 9 months to date. Cytokine release syndrome (CRS) 1 was experienced while no immune effector cell-associated neurotoxicity syndrome (ICANS) was found. In addition, CAR copy number peaked at 350, 758 copies/μg on day 6. This case report of clinical treatment of T-ALL with anti-CD7 CAR-T cells prepared using a retroviral vector without gene editing and combined with chemotherapy, which demonstrated that the RV-based anti-CD7 CAR-T cells had good therapeutic effect and high safety in triple-refractory T-ALL patients.

ABSTRACT Background With the increasing use of lung cancer screening, the detection of ground glass nodules (GGNs) has risen. However, the natural course of GGNs and their relationship to pathologic features remains unclear. Differentiating between invasive and pre‐invasive lesions based on GGN growth may improve clinical intervention timing. Ki‐67, a proliferation marker, holds value in assessing tumor malignancy. This study analyzes the association between GGN growth, pathology, and Ki‐67 expression to provide new insights into early‐stage lung cancer management. Methods We retrospectively evaluated 183 GGNs with at least two preoperative CT scans. Nodule location, type, natural course, and volume doubling time (VDT) were compared between invasive adenocarcinoma (IAC) and pre‐IAC groups. We also assessed differences in Ki‐67 expression and correlated VDT with Ki‐67 levels. Results A total of 183 nodules were finally included; gender, nodule location, smoking history, and duration of follow‐up did not differ between the IAC group and the pre‐IAC group, whereas age was statistically different between the two groups. Of the 183 nodules, 52 showed growth and the predominant pathologic type was IAC, these IACs showed more PSN in nodule type, while the IAC group showed more significant differences in nodule type, nodules growth, and VDT than the pre‐IAC group. There were also differences in pathologic type and VDT between different Ki‐67 expression groups, and Ki‐67 expression gradually increased as VDT decreased. Conclusion Lung adenocarcinoma (LUAD) presenting as GGNs exhibit distinct natural courses among pathologic subtypes. VDT effectively distinguishes these growth characteristics, with IACs showing shorter VDT. The significant correlation between VDT and Ki‐67 expression suggests that combining these parameters may provide valuable insights into the biological behavior and invasiveness of LUAD.

ABSTRACT Background In the era of novel agents, the clinical outcomes of induction treatment and the impact of the number of high‐risk cytogenetic abnormalities (HRA) in newly diagnosed multiple myeloma (NDMM) need to be explored. Objective Through this study, we aim to analyze the effectiveness of different induction treatments and explore the survival outcomes of patients with varying numbers of HRA. Methods A total of 734 patients from seven medical centers were included in our study. Results Patients in the CD38 monoclonal antibody or IMiDs plus proteasome inhibitors (PI) groups had significantly superior overall survival (OS) and progression‐free survival (PFS) compared to those receiving IMiDs or PI alone. Additionally, the CD38 monoclonal antibody conferred a PFS advantage over IMiDs plus PI. Patients with ≥ 2 high‐risk cytogenetic abnormalities (HRA) exhibited an extremely poor prognosis and should be considered ultra‐high‐risk individuals in multiple myeloma (MM). The CD38 monoclonal antibody, transplantation, and achieving minimal residual disease (MRD) negativity only partly mitigated the poor prognosis in patients with HRA. Furthermore, patients with 1q21 gain/amplification (1q21+) only had a significantly worse prognosis compared to patients without HRA, and those with 1q21+ plus del17p or t(4;14) exhibited an inferior prognosis compared to those with 1q21+ alone. Conclusion Our results suggested that double‐hit multiple myeloma was associated with extremely poor survival outcomes, and more effective treatments needed to be explored for this particular subtype of MM.

Chimeric antigen receptor T (CAR-T)-cell therapy targeting B-cell maturation antigen (BCMA) is currently one of the promising treatment methods for relapsed/refractory multiple myeloma (MM). Herein, this study is a case report on a 41-year-old male patient with MM. Unfortunately, he still developed multidrug-resistant, refractory, and bone marrow suppression after receiving multiline high-intensity chemotherapy. After a detailed evaluation, the physician recommended autologous hematopoietic stem cell transplantation (ASCT) support, followed by sequential immunotherapy with autologous anti- BCMA CAR-T cells. The CAR-T product is a novel anti-BCMA CAR-T based on Retrovirus vectors (RV). It was worth noting that the patient achieved VGPR (very good partial remission) one month after infusion of anti-BCMA CAR-T cells. Recent tests have found that the M protein was no longer detectable and the patient has achieved CR (complete response). Although grade 3 cytokine release syndrome (CRS) appeared, the symptom was well controlled and immune effector cell-associated neurotoxicity syndrome (ICANS) did not occur. This was the first case report of RV prepared anti-BCMA CAR-T cells combined with ASCT for the treatment of MM patient in clinical practice, indicating that the RV-based anti-BCMA-CAR-T cells with ASCT have excellent therapeutic efficacy and high safety in triple-refractory MM patients.

Abstract Background Mechanism underlying the malignant progression of precancer to early-stage lung adenocarcinoma (LUAD) as well as their indolence nature remains elusive. Methods Single-cell RNA sequencing (scRNA) with simultaneous T cell receptor (TCR) sequencing on 5 normal lung tissues, 3 precancerous and 4 early-stage LUAD manifested as pulmonary ground-glass nodules (GGNs) were performed. Results Through this integrated analysis, we have delineated five key modules that drive the malignant progression of early-stage LUAD in a disease stage-dependent manner. These modules are related to cell proliferation and metabolism, immune response, mitochondria, cilia, and cell adhesion. We also find that the tumor micro-environment (TME) of early-stage LUAD manifested as GGN are featured with regulatory T (Tregs) cells accumulation with three possible origins, and loss-functional state (decreased clonal expansion and cytotoxicity) of CD8 + T cells. Instead of exhaustion, the CD8 + T cells are featured with a shift to memory phenotype, which is significantly different from the late stage LUAD. Furthermore, we have identified monocyte-derived macrophages that undergo a lipid-phenotype transition and may contribute to the suppressive TME. Intense interaction between stromal cells, myeloid cells including lipid associated macrophages and LAMP3 + DCs, and lymphocytes were also characterized. Conclusions Our work provides new insight into the molecular and cellular mechanism underlying malignant progression of LUAD manifested as GGN, and pave way for novel immunotherapies for GGN. Video Abstract

Glaesserella parasuis (G. parasuis) can elicit meningitis in pigs; however, the pathogenic mechanisms of meningitis induced by G. parasuis remain unclear. Long non-coding RNAs (lncRNAs) have been proven to play key roles in a variety of physiological and pathological processes. However, whether lncRNAs are involved in meningitis triggered by G. parasuis has not been investigated. In this study, we performed an integrative analysis of lncRNAs expression profiles in the porcine brain infected with G. parasuis using RNA-seq. The results showed that lncRNA expressions in G. parasuis-induced meningitis were modified, and a total of 306 lncRNAs exhibited significant differential expression, in which 176 lncRNAs were up-regulated and 130 lncRNAs were down-regulated. KEGG enrichment analysis demonstrated that the differentially expressed target mRNAs of affected lncRNAs in G. parasuis-infected porcine brain were mainly involved in the cell adhesion molecules (CAMs), Jak-STAT signaling pathway, PI3k-Akt signaling pathway, and TNF signaling pathway. The expression relationship between the most affected differential lncRNAs and their differential target mRNAs was visualized by a co-expression network. A protein-protein interaction network consisting of 12 differential targets was constructed using STRING analysis. In addition, differential expressions of important lncRNAs were validated by qRT-PCR. lncRNA ALDBSSCT0000007362, ALDBSSCT0000001959, ALDBSSCT0000005529, MSTRG.2939.1, and MSTRG.32374.1 showed the same expression pattern with the lncRNA sequencing data. Our results demonstrated that G. parasuis could modify the lncRNA expression profiles in the porcine brain. To the best of our knowledge, this is the first report revealing the integrative analysis of lncRNA expression profiles in G. parasuis-induced meningitis, which could enhance important information to understand the inflammatory functions of lncRNAs involved in swine meningitis, and also provide a foundation for finding out novel strategies to prevent and treat meningitis in piglets triggered by G. parasuis.

Abstract The capacitance mismatch problem limits the accuracy improvement of high‐precision SAR ADCs (Successive Approximation Register Analog‐to‐Digital Converters). To address the capacitance array mismatch in SAR ADCs, this paper proposes a novel capacitor calibration scheme based on the Time‐to‐Digital Converter (TDC). This scheme achieves calibration accuracy as high as 0.01% and can be flexibly designed to meet the accuracy requirements of SAR ADCs. Simulation results indicate that the capacitance mismatch issue of a redundant capacitor 13‐bit SAR ADC can be completely eliminated, and the effective number of bits (ENOB) approach the ideal value of 13.18 bits. Additionally, the analog component of this scheme utilizes four inverter chains, two D flip‐flops, and four counters, without requiring a large area for auxiliary calibration capacitors.

Background: Recurrence and metastasis are the main causes of non-small cell lung cancer (NSCLC)-related death. CD146 has been identified as a potential risk factor for poor prognosis, closely related to the distant metastasis and drug resistance in various cancers. However, the clinical significance of CD146 in NSCLC requires further investigation. Materials and Methods: This study explored the correlation between CD146 expression and clinical variables using tumor tissue samples collected from our hospital. CD146 expression levels in NSCLC cell lines and tissues were assessed and compared using immunohistochemistry, real-time polymerase chain reaction (RT-qPCR), flow cytometry, and western blot analysis. The invasion and migration capabilities of tumor cells were determined using transwell and wound healing assays. The levels of proteins related to epithelial-mesenchymal transition (EMT) as well as the underlying PI3K/Akt signaling pathway was measured by western blotting. Results: We discovered that CD146 expression is significantly associated with the EMT signaling pathway. High CD146 expression predicted lymph node metastasis, metastasis to distant organs, advanced Tumor, Node, Metastasis (TNM) staging, and poor survival in NSCLC patients. Wound healing and transwell assays showed that knocking down CD146 significantly suppressed cell migration along with cell invasion in NSCLC, whereas overexpressing CD146 notably enhanced these processes. Western blot analysis revealed significantly reduced levels of N-cadherin, vimentin, snail, twist, PI3K, and AKT phosphorylation in shCD146 H460 cells compared to vector control cells. Treatment with PI3K inhibitor PI3K-IN-1 increased E-cadherin expression levels but reduced N-cadherin, Twist, Vimentin, PI3K, and AKT phosphorylation levels in pcDNA3.1-CD146 A549 cells compared with the vector control cells. Conclusions: CD146 expression acts as a prognostic risk factor for adverse outcomes in NSCLC, promoting invasion and metastasis by activating the EMT through the PI3K/Akt signaling pathway. These findings underscore the potential therapeutic strategies targeting CD146, offering new treatment options for NSCLC patients, especially those at risk of metastasis.

This comprehensive systematic review and meta-analysis assessed the prevalence of Achilles tendinopathy (AT) in physical exercise (PE). Specifically, we estimate the overall risk of AT in physical exercise and compare sport-specific estimates of AT risk. PubMed, Web of Science, Cochrane Library, and SPORTDiscus were searched before the 1st of October 2021. Random-effects, subgroup analysis, sensitivity analysis and meta-regressions were conducted, involving 16 publications. This meta-analysis found that the overall prevalence of AT was 0.06 (95%CI, 0.04–0.07). The prevalence of Achilles tendon rupture was 0.03 (95%CI, 0.02–0.05). Subgroup analysis showed that the prevalence of AT increased with age, the highest among the group aged over 45 (0.08; 95%CI, 0.04–0.11), and the lowest among the group under 18 years old (0.02; 95%CI, 0.01–0.03). The gymnastics and ball games had the highest prevalence of AT, at (0.17; 95%CI, 0.14–0.20) and (0.06; 95%CI, 0.02–0.11), respectively. The prevalence of AT in athletes (0.06; 95%CI, 0.04–0.08) was higher than that of amateur exercisers (0.04; 95%CI, 0.02–0.06) and there was no difference in the prevalence of AT between males and females. There are differences in the prevalence of AT in different ages, sport events and characteristics of participants. This systematic review and meta-analysis suggested that it was necessary to pay more attention to AT in people who were older or engaged in gymnastics.

Although numerous studies have explored the relationship between selenium intake and thyroid diseases, few epidemiological studies have investigated the association between selenium intake and thyroid hormones. Therefore, we conducted this analysis to investigate the association between dietary selenium intake and thyroid hormones. Our sample included 5,575 adults (age ≥ 20) years from the National Health and Nutrition Examination Survey (NHANES) 2007–2012. Thyroid hormones, including total triiodothyronine (T3), total thyroxine (T4), free T3 (FT3), free T4 (FT4), and thyroid-stimulating hormone (TSH), were detected. Multivariable linear regression models showed that log10-transformed selenium intake (LogSe) was negatively correlated with TT4 (β = −0.383, 95% CI: −0.695, −0.070) and TT4/TT3 (β = −0.003, 95% CI: −0.006, −0.0004) in U.S. adults. Besides, additional stratified analyses by sex demonstrated that LogSe was negatively associated with TT4 (β = −0.007, 95% CI: −0.013, −0.001) and TT4/TT3 (β = −0.664, 95% CI: −1.182, −0.146) and positively associated with FT4/TT4 (β = 0.031, 95% CI: 0.004, 0.059) in male adults. Meanwhile, subgroup analysis by iodine status showed that LogSe was negatively associated with TT4 (β = −0.006, 95% CI: −0.011, −0.002), FT4/FT3 (β = −0.011, 95% CI: −0.023, −0.00002) and TT4/TT3 (β = −0.456, 95% CI: −0.886, −0.026) in iodine sufficiency but not in iodine deficiency adults. Our results demonstrated that the increased dietary selenium intake was negatively correlated with TT4 and TT4/TT3 in U.S. adults. Furthermore, the association between dietary selenium intake and thyroid hormones was more pronounced in males and iodine sufficiency adults.

AbstractThe reservoir property of tight sandstones is closely related to the provenance and diagenesis, and multiprovenance system and complex diagenesis are developed in Hangjinqi area. However, the relationship between provenance, diagenesis, and physical characteristics of tight reservoirs in Hangjinqi area has not yet been reported. The Middle Permian Lower Shihezi Formation is one of the most important tight gas sandstone reservoirs in the Hangjinqi area of Ordos Basin. This research compared the diagenesis-porosity quantitative evolution mechanisms of Lower Shihezi Formation sandstones from various provenances in the Hangjinqi area using thin-section descriptions, cathodoluminescence imaging, X-ray diffraction (XRD), scanning electron microscopy (SEM), and homogenization temperature of fluid inclusions, along with general physical data and high-pressure mercury intrusion (HPMI) data. The sandstones mainly comprise quartzarenite, sublitharenite, and litharenite with low porosity and low permeability and display obvious zonation in the content of detrital components as a result of multiprovenance. Pore space of those sandstone mainly consists of primary pores, secondary pores, and microfractures, but their proportion varies in different provenances. According to HPMI, the order of the pore-throat radius from largest to smallest is central provenance, eastern provenance, and western provenance, which is consistent with the change tend of porosity (middle part>northern part>western part) in Hangjinqi region. The diagenetic evolution path of those sandstones is comparable, with compaction, cementation, dissolution, and fracture development. The central provenance has the best reservoir quality, followed by the eastern provenance and the western provenance, and this variation due to the diverse diagenesis (diagenetic stage and intensity) of different provenances. These findings reveal that the variations in detrital composition and structure caused by different provenances are the material basis of reservoir differentiation, and the main rationale for reservoir differentiation is varying degrees of diagenesis during burial process.

Enterocytozoon bieneusi is a zoonotic pathogen commonly found in humans and animals all over the world. Here, we investigated the occurrence and genotype constitute of E. bieneusi among the individuals from Haikou city of Hainan, China. A total of 1,264 fecal samples of humans were collected, including 628 samples from patients with diarrhea (325 adults and 303 children) and 636 samples from the asymptomatic population (383 college students and 253 kindergarten children). E. bieneusi was detected using nested polymerase chain reaction (PCR) amplification of the internal transcribed spacer (ITS) region. A phylogenetic tree was constructed using a neighbor-joining tree construction method. The overall prevalence of E. bieneusi was 3.7% (47/1,264), while it was 5.6% in the patients with diarrhea (5.8% in adults and 5.3% in children) and 1.9% in the asymptomatic population (2.9% in college students and 0.4% in kindergarten children). The prevalence of E. bieneusi in humans with diarrhea was significantly higher than that in the asymptomatic population (χ2 = 36.9; P < 0.05). A total of 28 genotypes were identified, including ten known genotypes: CHG2 (n = 3), CHG3 (n = 5), CHG5 (n = 10), CM21 (n = 1), EbpA (n = 1), EbpC (n = 1), PigEBITS4 (n = 1), PigEBITS7 (n = 1), SHR1 (n = 4), Type IV (n = 2), and 18 novel genotypes (HNH-1 to HNH-18; one each). All these genotypes were categorized into three groups, including group 1 (n = 6), group 2 (n = 14), and group 13 (n = 8). This was the first study on the identification of E. bieneusi among humans in Hainan, China. The correlation between E. bieneusi infection and diarrhea was observed. The high diversity and distinctive distribution of E. bieneusi genotypes found in this study reflected the unique epidemic genetic characteristics of E. bieneusi in humans living in Hainan.

In the original publication [...]

To date, little is known about the regulatory landscape of the pig genome. Here, the authors characterize cis-regulatory elements in the pig genome using RNA-seq, ChIP-Seq and ATAC-seq, finding a higher degree of usage conservation between pig and human than mouse and human.

Abstract Background The CD4 protein is an important surface marker of T lymphocytes, which can mediate the antigen presentation process by interacting with MHC II and TCR molecules in human and mouse. Results In this study, two haplotypes (A and B) of the CD4 gene were found within Chinese indigenous and Western commercial pig breeds. These two haplotypes were defined by 22 fully linked SNPs in the CDS region of the CD4 gene. The expression level and localization of the CD4 protein were significantly different between haplotypes A and B. Transcriptome analysis revealed that the immune response-related genes and signaling pathways were down-regulated in genotype AA. Finally, three linked functional SNPs were identified, which affected the expression level and membrane localization of the CD4 protein in pigs. These three SNPs led to the replacements of two amino acids in the IgV1 domain of the CD4 protein, and related to the function of the CD4 protein in the immune response. Conclusion These three linked SNPs were the key functional mutation sites in the CD4 gene, which played important roles in the immune response, and could be utilized as new molecular markers in breeding for disease resistance in pigs.

Abstract Background Rodents, globally overpopulated, are an important source for zoonotic disease transmission to humans, including Enterocytozoon bieneusi (one of the most prevalent zoonotic pathogens). Here, we studied the prevalence and performed genetic analyses of E. bieneusi in rodents from the Hainan Province of China. Methods A total of 603 fresh fecal samples were gathered from 369 wild rats, 117 bamboo rats, 93 Asiatic brush-tailed porcupine and 24 red-bellied squirrels. The wild rats were identified to the species level by amplification of a 421-bp region of the cytb gene from fecal DNA using PCR. Genotype analysis was performed by amplification of the internal transcribed spacer (ITS) region of rDNA of E. bieneusi using PCR. Results Seven wild rat species were identified. The average rate of infection with E. bieneusi was 15.8% (95/603) with 18.7% (69/369) in wild rats, 11.9% (25/210) in farmed rodents and 4.2% (1/24) in red-bellied squirrels. Sixteen E. bieneusi genotypes were identified, including 9 known genotypes (D, Type IV, PigEBITS7, Peru8, Peru11, ESH02, S7, EbpA and CHG5), and 7 novel genotypes (HNR-I to HNR-VII). Genotype D (44.2%, 42/95) predominated, followed by PigEBITS7 (20.0%, 19/95), HNR-VII (15.8%, 15/95), Type IV (5.3%, 5/95), HNR-III (2.1%, 2/95), HNR-VI (2.1%, 2/95) and each of the remaining 10 genotypes (1.1%, 1/95). The phylogenetic analysis of the ITS region of E. bieneusi divided the identified genotypes into the following four groups: Group 1 (n = 13), Group 2 (n = 1), Group 12 (n = 1), and the novel Group 13 (n = 1). Conclusions To our knowledge, this is the first report on the identification of E. bieneusi in rodents from Hainan, China. The zoonotic potential of the identified E. bieneusi genotypes suggested that the rodents poses a serious threat to the local inhabitants. Thus, measures need to be taken to control the population of wild rats in the areas investigated in this study, along with identification of safe methods for disposal of farmed rodent feces. Additionally, the local people should be made aware of the risk of disease transmission from rodents to humans.

Abstract miRNAs reportedly participate in various biological processes, such as skeletal muscle proliferation and differentiation. However, the regulation of differentially expressed (DE) miRNAs and their function in myogenesis remain unclear. Herein, miRNA expression profiles and regulation during C2C12 differentiation were analyzed in relation to chromatin states by RNA-seq, ATAC-seq, and ChIP-seq. We identified 19 known and nine novel differentially expressed miRNAs at days 0, 1, 2, and 4. The expression of the differentially expressed miRNAs was related to the chromatin states of the 113 surrounding open chromatin regions defined by ATAC-seq peaks. Of these open chromatin regions, 44.25% were colocalized with MyoD/MyoG binding sites. The remainder of the above open chromatin regions were enriched with motifs of the myoblast-expressed AP-1 family, Ctcf, and Bach2 transcription factors (TFs). Additionally, the target genes of the above differentially expressed miRNAs were enriched primarily in muscle growth and development pathways, especially the Hippo signaling pathway. Moreover, via combining a loss-of-function assay with Q-PCR, western blotting, and immunofluorescence, we confirmed that the Hippo signaling pathway was responsible for C2C12 myoblast differentiation. Thus, our results showed that these differentially expressed miRNAs were regulated by chromatin states and affected muscle differentiation through the Hippo signaling pathway. Our findings provide new insights into the function of these differentially expressed miRNAs and the regulation of their expression during myoblast differentiation.

The coronavirus disease 2019 (COVID-19) pandemic has led to 4,255,892 deaths worldwide. Although COVID-19 vaccines are available, mutant forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have reduced the effectiveness of vaccines. Patients with cancer are more vulnerable to COVID-19 than patients without cancer. Identification of new drugs to treat COVID-19 could reduce mortality rate, and traditional Chinese Medicine(TCM) has shown potential in COVID-19 treatment. In this study, we focused on lung adenocarcinoma (LUAD) patients with COVID-19. We aimed to investigate the use of curcumol, a TCM, to treat LUAD patients with COVID-19, using network pharmacology and systematic bioinformatics analysis. The results showed that LUAD and patients with COVID-19 share a cluster of common deregulated targets. The network pharmacology analysis identified seven core targets (namely, AURKA, CDK1, CCNB1, CCNB2, CCNE1, CCNE2, and TTK) of curcumol in patients with COVID-19 and LUAD. Clinicopathological analysis of these targets demonstrated that the expression of these targets is associated with poor patient survival rates. The bioinformatics analysis further highlighted the involvement of this target cluster in DNA damage response, chromosome stability, and pathogenesis of LUAD. More importantly, these targets influence cell-signaling associated with the Warburg effect, which supports SARS-CoV-2 replication and inflammatory response. Comparative transcriptomic analysis on in vitro LUAD cell further validated the effect of curcumol for treating LUAD through the control of cell cycle and DNA damage response. This study supports the earlier findings that curcumol is a potential treatment for patients with LUAD and COVID-19.

The macrophage CD163 surface glycoprotein is a member of the SRCR family class B, which has been identified as the key trigger in host–pathogen interactions, but its specific roles in sensing Glaesserella parasuis (G. parasuis) infection are largely unknown. Here, we investigated porcine CD163 in mediating the adhesion and immune response of G. parasuis using in vitro host–bacteria interaction models. CD163-overexpressing Chinese hamster ovary K1 cells (CHO-K1) showed obvious subcellular localization in the cytoplasm, especially in the cytomembrane. Although detection using scanning electron microscopy (SEM) confirmed the bacterial adhesion, there was no significant difference in the adhesion of G. parasuis to CHO-K1 cells between the presence and absence of CD163. In addition, similar results were observed in 3D4/21 cells. Meanwhile, bindings of G. parasuis to nine synthetic peptides, the bacterial binding motifs within SRCR domains of CD163, were weak based on a solid-phase adhesion assay and agglutination assay. Moreover, CD163 had no effect on the expression of G. parasuis-induced inflammatory cytokines (IL-6, INF-γ, IL-10, IL-4 and TGF-β) in CHO-K1 cells. In conclusion, these findings indicate that porcine CD163 plays a minor role in sensing G. parasuis infection.

Deoxynivalenol (DON) is a kind of Fusarium toxin that can cause a variety of toxic effects. DON is mainly metabolized and detoxified by the liver. When the concentration of DON exceeds the metabolic capacity of the liver, it will trigger acute or chronic damage to the liver tissue. Previous studies demonstrated that bone marrow mesenchymal stem-cell-secreted exosomes (BMSC-exos) reduce liver injury. Therefore, we issue a hypothesis that in vitro-cultured rat BMSC-secreted exos could ameliorate liver damage after 2 mg/kg bw/day of DON exposure. In total, 144 lipids were identified in BMEC-exos, including high polyunsaturated fatty acid (PUFA) levels. BMSC-exos treatment alleviated liver pathological changes and decreased levels of alanine aminotransferase, aspartate aminotransferase, inflammatory factors interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and lipid peroxidation. Otherwise, low or high BMSC-exos treatment obviously changes DON-induced hepatic oxylipin patterns. According to the results from our correlation network analysis, Pearson correlation coefficient analysis, and hierarchical clustering analysis, the top 10% oxidized lipids can be classified into two categories: one that was positively correlated with copper–zinc superoxide dismutase (Cu/Zn SOD) and another that was positively correlated with liver injury indicators. Altogether, BMSC-exos administration maintained normal liver function and reduced oxidative damage in liver tissue. Moreover, it could also significantly change the oxylipin profiles under DON conditions.

Abstract Background To investigate the prevalence of cardiovascular disease (CVD) risk factors and assess the 10-year risk of CVD in non-menopausal and postmenopausal women with type 2 diabetes mellitus (T2DM). Methods A total of 569 patients with T2DM at a Chinese tertiary hospital were investigated using the Framingham Risk Score (FRS). We evaluated the 10-year risk of CVD, clinical and menopause characteristics in all subjects. Results Among the 569 diabetic patients, the incidence of smoking, dyslipidemia, hypertension, overweight or obesity, and nonalcoholic fatty liver disease (NAFLD) was 0.7, 36.2, 38.1 56.6 and 58.2%, respectively. The usage rate of hypoglycemic agents, antihypertensive agents, lipid modulators and antithrombotic drugs was 88.6, 78.3, 50.0 and 27.1%, respectively. However, only 1.2% of inpatients achieved the three target goals for the control of blood glucose (HbA1c

Wild rats (Rattus spp.) carry many zoonotic pathogens including Cryptosporidium. Due to the close proximity of rats to humans in urban environments, the potential for disease transmission is high. Cryptosporidium is a protozoan parasite which when ingested causes serious human illness. Despite its importance, genetic characterization of Cryptosporidium in wild rats in the Hainan province of China has not been performed. In this study, we analyzed the occurrence and genetics of Cryptosporidium in wild rats from Hainan, China. From December 2017 to October 2018, 150 wild rats were captured and fresh fecal material was collected from intestinal sections. Rat species were identified by PCR-based amplification and analysis of the vertebrate cytochrome b (cytb) gene. Cryptosporidium was examined by PCR amplification of the partial small subunit of ribosomal DNA (SSU rDNA). C. viatorum were subtyped by PCR analysis of the gp60 gene. A total of four rat species were identified including Asian house rats (Rattus tanezumi) (n = 46), brown rats (Rattus norvegicus) (n = 56), Edward's long-tailed rats (Leopoldamys edwardsi) (n = 38) and muridae (Niviventer fulvescens) (n = 10), with Cryptosporidium positive rates of 73.9%, 28.6%, 55.3% and 40.0%, respectively (average infection rate: 50.0%, 75/150. Sequence analysis confirmed the presence of four Cryptosporidium species and two genotypes including C. viatorum (n = 11); C. occultus (n = 2); C. muris (n = 1); and C. erinacei (n = 1); rat genotypes III (n = 13) and IV (n = 47). Three novel subtypes of C. viatorum were identified in 6 of the 11 infected Edward's long-tailed rats: XVcA2G1a (n = 4), XVcA2G1b (n = 1) and XVdA3 (n = 1). The identification of human pathogenic C. viatorum and zoonotic C. occultus, C. muris and C. erinacei, suggested that wild rats infected with Cryptosporidium pose a threat to human health. Taken together, these findings highlight the need to control the rat population in Hainan, China. The need to improve the public awareness of the risk of disease transmission from wild rats to humans is also highlighted. Keywords: Cryptosporidium, Wild rat, Molecular detection, Zoonotic, Public health

Abstract Background Cryptosporidium is an important zoonotic parasite that is commonly found in non-human primates (NHPs). Consequently, there is the potential for transmission of this pathogen from NHPs to humans. However, molecular characterization of the isolates of Cryptosporidium from NHPs remains relatively poor. The aim of the present work was to (i) determine the prevalence; and (ii) perform a genetic characterization of the Cryptosporidium isolated from captive Macaca fascicularis and M. mulatta on Hainan Island in southern China. Methods A total of 223 fresh fecal samples were collected from captive M. fascicularis (n = 193) and M. mulatta (n = 30). The fecal specimens were examined for the presence of Cryptosporidium spp. by polymerase chain reaction (PCR) and sequencing of the partial small subunit (SSU) rRNA gene. The Cryptosporidium-positive specimens were subtyped by analyzing the 60-kDa glycoprotein (gp60) gene sequence. Results Cryptosporidium spp. were detected in 5.7% (11/193) of M. fascicularis. All of the 11 Cryptosporidium isolates were identified as C. hominis. Subtyping of nine of these isolates identified four unique gp60 subtypes of C. hominis. These included IaA20R3a (n = 1), IoA17a (n = 1), IoA17b (n = 1), and IiA17 (n = 6). Notably, subtypes IaA20R3a, IoA17a, and IoA17b were novel subtypes which have not been reported previously. Conclusions To our knowledge, this is the first reported detection of Cryptosporidium in captive M. fascicularis from Hainan Island. The molecular characteristics and subtypes of the isolates here provide novel insights into the genotypic variation in C. hominis.

AbstractThe physical property heterogeneity of tight sandstones was mainly caused by complex alteration of various diagenesis combinations during burial process. However, diagenetic evolution of different diagenesis combinations which generally result in the strong difference and heterogeneity of physical property and pore structure is rarely well understood. The Middle Permian lower Shihezi Formation is one of the most important tight gas sandstone reservoirs in the Hangjinqi area of Ordos Basin, China. The reservoir heterogeneity of lower Shihezi Formation, which was caused by the differential diagenesis combination, is crucial to efficient exploration and development. Evolution mechanism of differential diagenesis combination and its effect on the reservoir quality in the tight lower Shihezi Formation sandstone in the Hangjinqi area of Ordos Basin was investigated by means of thin-section description, cathodoluminescence (CL) imaging, X-ray diffraction (XRD), scanning electron microscopy (SEM), and homogenization temperature of fluid inclusions. The lower Shihezi Formation sandstones can be divided into four diagenesis combination types according to the reservoir characteristics and diagenetic relationship. The main diagenetic sequence was mechanical compaction-chlorite rim-early pore-filling calcite cementation-dissolution-authigenic kaolinite-quartz cementation-late calcite cementation. Differential diagenesis combination was mainly controlled by the petrological characteristics, microfacies, and fault. Low content of rock fragment and high content of detrital quartz were beneficial to the compaction resistance and cementation. The moderate content of pore-filling calcite was conducive to pore space protection and feldspar dissolution. The faults control dissolution and differential diagenesis combination by influencing the migration of acid fluids. Moderate compaction-moderate cementation-moderate dissolution type (BBB type) and weak compaction-moderate cementation-strong dissolution type (CBA type) were in favour of high-quality reservoir development.

As a commonly used turfgrass, Kentucky bluegrass (Poa pratensis L.) (KBG) has many commercially available cultivars for production. After several years of screening, two new lines were obtained (‘KBG03’ and ‘KBG04’), which have high tolerance to summer. The study showed that the two lines revealed similar morphological characteristics, with light green leaf color, narrow leaf blade, high plant height and light 1,000-grain weight. A total of 400 random amplified polymorphic DNA (RAPD) primers and 256 sequence-related amplified polymorphism (SRAP) primer combinations were screened among the two lines and other 4 imported commercial cultivars. The percentages of polymorphic sites were 65.5% (RAPD) and 22.6% (SRAP) respectively. By cluster analysis of RAPD and SRAP data, the dendrogram at a similarity of 0.29 gave two main clusters, of which one group had 4 commercial cultivars, and the other had the two new breeding lines. Furthermore, one specific band of ‘KBG04’ was successfully converted into a dominant sequence characterized amplified region marker (SCAR196). Then the SCAR marker was verified by 39 KBG DNA samples, including imported varieties, domestic varieties and self-breeding lines of our laboratory, and it exhibited high consistency with the original RAPD polymorphic amplification. The results showed that the SCAR marker can be used to distinguish the new line ‘KBG04’ from numerous KBG germplasms, which would be useful for cultivar identification and property rights protection in the future.

The development and clinical application of 2-methoxyestradiol (2-ME) as a new type of antitumor drug are limited due to its poor solubility, rapid metabolism in vivo, and large oral dosage. 2-ME-loaded pH-sensitive liposomes (2-ME-PSLs) was prepared containing the lipids, Lipoid E-80 (E-80), cholesteryl hemisuccinate (CHEMS), and cholesterol (CHOL) via thin-film ultrasonic dispersion. First, preparation conditions of 2-ME-PSLs were optimized by orthogonal test. Then 2-ME-PSL was characterized, and the release behavior and stability of 2-ME-PSL in vitro were evaluated. The optimal preparation conditions for 2-ME-PSLs were as follows: 2-ME : E-80+CHEMS 1:15; CHOL : E-80+CHEMS 1:5; ultrasonication time 20 minutes. The mean particle size, PDI, zeta potential, and entrapment efficiency (EE) of 2-ME-PSLs were 116 ± 9 nm, 0.161 ± 0.025, −22.4 ± 1.7 mV, and 98.6 ± 0.5%, respectively. As viewed under a transmission electron microscope, 2-ME-PSLs were well dispersed and almost spherical. They exhibited significant pH-sensitive properties and were fairly stable when diluted with a physiological solution. In conclusion, 2-ME-PSLs were successfully prepared and possessed a favorable pH sensitivity and good dissolution stability with a normal solution.