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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 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

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.

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 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.

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.

Objective To examine the association of carotid artery plaque with the incident coronary heart disease and stroke events in Chinese patients and explore whether the association differs between patients with and without hyperglycemia. Methods We evaluated plaque, and blood pressure, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting serum insulin, fasting plasma glucose, 2 h postprandial glucose and Homeostasis model assessment of insulin resistance in 253 Chinese patients. T-test and X2 test were used to compare the clinical characteristics and Binary logistic regression was applied to analyze the association of coronary heart disease and stroke between patients with and without hyperglycemia. Results Among 253 patients, 162 patients had hyperglycemia (i. e., diabetes, impaired glucose regulation and stress induced hyperglycemia) and 155 (61.3 %) patients had plaque. Fasting plasma glucose, 2 h postprandial glucose and Homeostasis model assessment of insulin resistance, triglycerides, plaque were significantly higher in the hyperglycemia group than non-hyperglycemia. The incident coronary heart disease and stroke events in patients with plaque were 2.254 (95 %CI,1.203-4.224) and 2.437 (95 %CI,1.042-5.701) times higher than those without plaque, respectively. Among hyperglycemia subgroup, plaque was an independent risk factor for coronary heart disease (OR, 3.075, 95% CI, 1.353 - 6.992) and stroke (OR,3.571,95 %CI, 1.460-8.737). The slopes (associations between coronary heart disease/stroke and plaque) were steeper in the hyperglycemia group than those in the non-hyperglycemia group (coronary heart disease OR,3.075 vs. 2.614; stroke OR, 3.571 vs. 3.307). Conclusions The incident coronary heart disease and stroke events in patients with plaque were higher than those without plaque, and this difference was more pronounced for patients with hyperglycemia vs. those without hyperglycemia. [ABSTRACT FROM AUTHOR]

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.

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 FROM AUTHOR]

Comprehensive functional genome annotation is crucial to elucidate the molecular mechanisms of agronomic traits in livestock, yet systematic functional annotation of the sheep genome is lacking. Here, we generated 92 transcriptomic and epigenomic data sets from nine major tissues, along with whole‐genome data from 2357 individuals across 29 breeds worldwide, and 4006 phenotypic data related to tail fat weight. We constructed the first multi‐tissue epigenome atlas in terms of functional elements, chromatin states, and their functions and explored the utility of the functional elements in interpreting phenotypic variation during sheep domestication and improvement. Particularly, we identified a total of 753,723 nonredundant functional elements, with over 60% being novel. We found tissue‐specific promoters and enhancers related to sensory abilities and immune response that were highly enriched in genomic regions influenced by domestication, while longissimus dorsi tissue‐specific active enhancers and tail fat tissue‐specific active promoters were highly enriched in genomic regions influenced by breeding and improvement. Notably, a variant, Chr13:51760995A>C, located in an enhancer region, was identified as a causal variant for tail fat deposition based on multi‐layered data sets. Overall, this research provides foundational resources and a successful case for future investigations of complex traits in sheep through the integration of multi‐omics data sets. Highlights: Generated 92 transcriptomic and epigenomic data sets from nine sheep tissues, establishing the first multi‐tissue epigenome atlas for functional genomic elements.Identified 753,723 nonredundant functional elements, with over 60% being novel, including tissue‐specific promoters and enhancers linked to sensory abilities, immune response, and tail fat deposition.Discovered a novel variant, Chr13:5176099A>C, located in an enhancer region, pinpointed as a causal variant for tail fat deposition using multi‐layered data sets. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 < 0.05) reduced, spore production and germination rates could be significantly (p < 0.05) increased. However, pathogenicity tests confirmed a severe fitness cost associated with tebuconazole resistance, as all of the mutants completely loss the ability to infect host tissue. Furthermore, in general the resistant mutants were found to have increased sensitivity to abiotic stress, such as ionic and osmotic stress, though not to Congo red and oxidative stress, to which they were more tolerant. Meanwhile, molecular analysis identified several point mutations in the CYP51 genes of the mutants, which resulted in two substitutions (I281T, and T314A) in the predicted sequence of the FgCYP51A subunit, as well as seven (S195F, Q332V, V333L, L334G, M399T, E507G, and E267G) in the FgCYP51C subunit. In addition, it was also noted that the expression of the CYP51 genes in one of the mutants, which lacked point mutations, was significantly up-regulated in response to tebuconazole treatment. Conclusions: These results provide useful data that allow for more rational use of tebuconazole in the control of F. graminearum, as well as for more effective monitoring of fungicide resistance in the field. [ABSTRACT FROM AUTHOR]

Glaesserella parasuis (GPS) can cause severe systemic inflammation in pigs, resulting in huge economic losses to the pig industry. At present, no effective method is available for the prevention and control of GPS infection. Molecular breeding for disease resistance is imminent, but disease-resistance genes have not been identified. To study the mechanism of systemic acute inflammation caused by GPS, we established three in vitro infection models (3D4/21 cells, PK15 cells, and PAVEC cells) according to its infection path. There was no significant difference in apoptosis among the three kinds of cells after 12 h of continuous GPS stimulation, while inflammatory factors were significantly upregulated. Subsequent transcriptome analysis revealed 1969, 1207, and 3564 differentially expressed genes (DEGs) in 3D4/21 cells, PK15 cells, and PAVEC cells, respectively, after GPS infection. Many of the DEGs were predicted to be associated with inflammatory responses (C3, CD44, etc.); cell proliferation, growth and apoptosis; gene expression; and protein phosphorylation. Key signaling pathways, including S100 family signaling, bacteria and virus recognition, and pathogen-induced cytokine storm signaling, were enriched based on Ingenuity Pathway Analysis (IPA). Furthermore, a total of three putative transmembrane receptors and two putative G-protein-coupled receptors, namely F3, ICAM1, PLAUR, ACKR3, and GPRC5A, were identified by IPA among the three types of cells. ACKR3 and GPRC5A play pivotal roles in bacterial adhesion, invasion, host immune response and inflammatory response through the S100 family signaling pathway. Our findings provide new insights into the pathological mechanisms underlying systemic inflammation caused by GPS infection in pigs, and they lay a foundation for further research on disease-resistance breeding to GPS. [ABSTRACT FROM AUTHOR]

Purpose: There is no clear information in the literature about the relationship between the efficacy of CDK 4/6i combined with ET and HR positivity. However, we know that the longest overall survival was in the ER-strong positive/PR intermediate or strong positive groups. Therefore, we aimed to investigate CDK4/6i treatments that create positivity in HR. Methods: Patients with the diagnosis of HR+/HER2- MBC who were treated with CDK 4/6i and HR >10% were retrospectively evaluated. To analyze the role of HR positivity, ER was moderately positive (10-49%) and ER was strongly positive (50-100%); PR was grouped as moderately positive (10-49%) and PR strongly positive (50-100%). Results: Median follow-up of 150 patients included in the study was 15.2 months (95% CI, 2.1-40.9 months). The highest response in the whole group was obtained in the ER-strong positive/PR moderate or strong positive group, and the ER moderate positive/PR moderate or strong group. This was followed by the ER strong positive/PR negative group, and then the ER moderate positive/PR negative group. Although these advantages were not statistically significant, they were numerically higher (ORR: 83.8% vs. 83.3% vs. 77.4% vs. 62.5%, p=0.488, respectively). The highest survival in the whole group was achieved in the ER strong positive/PR moderate or strongly positive group, followed by the ER moderately positive/PR moderate or strongly positive group, the ER strongly positive/PR negative group followed by the ER moderate positive/PR negative group, respectively(p=0.410). However, these advantages were not statistically significant. Conclusion: As a result, HR+/HER2- MBC patients receiving CDK 4/6i combined with ET suggest that the percentage of HR positivity may have a predictive and prognostic role. [ABSTRACT FROM AUTHOR]

Climate change poses a significant threat to food security, necessitating a thorough examination across multiple dimensions. Establishing appropriate food security evaluation indicators that align with the evolving concept of food security is imperative. This study enhances food security evaluation by designing a multi-dimensional framework and analyzing the impact of climate variations across various regions from 2002 to 2021. By constructing a food security evaluation system that encompasses the production quantity and quality, sustainability, affordability, and resources, and utilizing the entropy method for accurate weighting, the impacts of climate variations on food security are accessed using a climate–economic model. The food security structure in China largely mirrors the regional division of grain, with the production quantity being the primary contributor. Overall, China's food security has generally demonstrated improvements across various dimensions, with the exception of production quality. Regarding climate change, which encompasses variations in mean states and climate extremes, the panel regression analysis uncovers a negative linear relationship between food security and temperature. Conversely, the impact of precipitation on food security is non-linear, manifesting as inverse U-shaped patterns. In regions with balanced production and consumption, both accumulated temperatures and extreme high temperatures have a negative linear effect on food security. On the other hand, both accumulated and extreme precipitation exhibit inverse U-shaped non-linear impacts on food security in the main production and main consumption regions. These findings highlight the intricate interplay between climate change, regional disparities, and food security in China, emphasizing the need to consider multi-dimensional factors and regional variations in addressing food security challenges. These insights are invaluable for policymaking and planning aimed at enhancing food security in China. [ABSTRACT FROM AUTHOR]

Tight sandstone and shale oil and gas are the key targets of unconventional oil and gas exploration in the lake-delta sedimentary systems of China. Understanding the coevolutionary diagenesis of sandstone and shale reservoirs is crucial for the prediction of reservoir quality, ahead of drilling, in such systems. Thin-section description, scanning electron microscopy (SEM), X-ray diffraction (XRD), fluid inclusion analysis, porosity and permeability tests, high-pressure mercury intrusion (HPMI) measurements and nuclear magnetic resonance tests (NMR) were used to reveal the coevolutionary diagenetic mechanisms of a sandstone and shale reservoir in the Lianggaoshan Formation of the Eastern Sichuan Basin, China. The thermally mature, organic-matter-rich, dark shale of layer3 is the most important source rock within the Lianggaoshan Formation. It started to generate abundant organic acids at the early stage of mesodiagenesis and produced abundant hydrocarbons in the early Cretaceous. Porewater with high concentrations of Ca2+ and CO32− entered the sandstone reservoir from dark shale as the shale was compacted during burial. Potassium feldspar dissolution at the boundary of the sandstone was more pervasive than at the center of the sandstone. The K+ released by potassium feldspar dissolution migrated from the sandstone into mudstone. Grain-rimming chlorite coats occurred mainly in the center of the sandstone. Some silica exported from the shale was imported by the sandstone boundary and precipitated close to the shale/sandstone boundary. Some intergranular dissolution pores and intercrystal pores were formed in the shale due to dissolution during the early stages of mesodiagenesis. Chlorite coats, which precipitated during eodiagenesis, were beneficial to the protection of primary pore space in the sandstone. Calcite cement, which preferentially precipitated at the boundary of sandstone, was not conducive to reservoir development. Dissolution mainly occurred at the early stage of mesodiagenesis due to organic acids derived from the dark shale. Calcite cement could also protect some primary pores from compaction and release pore space following dissolution. The porosity of sandstone and shale was mainly controlled by the thickness of sandstone and dark shale. [ABSTRACT FROM AUTHOR]

Glaesserella parasuis (G. parasuis) causes systemic infection in pigs, but its effects on skeletal muscle and underlying mechanisms are poorly understood. We investigated G. parasuis infection in colostrum-deprived piglets, observing decreased daily weight gain and upregulation of inflammatory factors in skeletal muscle. Muscle fiber area and diameter were significantly reduced in the treated group (n = 3) compared to the control group (n = 3), accompanied by increased expression of FOXO1, FBXO32, TRIM63, CTSL, and BNIP3. Based on mRNA and microRNA (miRNA) sequencing, we identified 1642 differentially expressed (DE) mRNAs and 19 known DE miRNAs in skeletal muscle tissues between the two groups. We predicted target genes with opposite expression patterns to the 19 miRNAs and found significant enrichment and activation of the FoxO signaling pathway. We found that the upregulated core effectors FOXO1 and FOXO4 were targeted by downregulated ssc-miR-486, ssc-miR-370, ssc-miR-615, and ssc-miR-224. Further investigation showed that their downstream upregulated genes involved in protein degradation were also targeted by the downregulated ssc-miR-370, ssc-miR-615, ssc-miR-194a-5p, and ssc-miR-194b-5p. These findings suggest that G. parasuis infection causes skeletal muscle atrophy in piglets through accelerated protein degradation mediated by the "miRNAs-FOXO1/4" axis, while further research is necessary to validate the regulatory relationships. Our results provide new insights into the understanding of systemic inflammation growth mechanisms caused by G. parasuis and the role of miRNAs in bacterial infection pathogenesis. [ABSTRACT FROM AUTHOR]

B Specifically, in the two pictures in Figure 2C, showing the results of the adhesion study using a Scanning Electron Microscope (SEM), the same original SEM picture was inadvertently used. b The corrected B Figure 2 b appears below. Figure Graph: Figure 2 The adhesion of G. parasuis to CHO-K1 cells with or without CD163 expression. (C) SEM micrograph showing the attachment of G. parasuis to the surface of CHO-K1 cells or CHO-K1CD163' cells after incubation for 6 h. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]