Search

Background: The carrying rate of thalassemia is high in Quanzhou city. However, there are few large-scale studies on the correlation analysis between genotype and phenotype of thalassemia in Quanzhou. In this study, the genotype and phenotype data of 1076 individuals with thalassemia in Quanzhou city were analyzed to provide reference data for screening and diagnosis of thalassemia in this region., Material and Methods: Reverse dot blot hybridization (RDB-PCR), Gap-PCR and nested PCR were used to detect the thalassemia genotype. Clinical and hematological parameters of 1076 individuals of thalassemia were collected to analyze the correlation between genotype and phenotype., Results: Among 2997 subjects, 1076 cases diagnosed as thalassemia gene carrier or patients, with detection rate 35.9 %, among which Southeast Asian deletion (-- SEA )/αα was the most common α-thalassemia genotype (48.4 %) and one rare genotype was detected: HKαα/-- SEA (0.1 %). Subjects with thalassemia alone showed the least severe symptoms of anemia with higher red blood cell count (RBC) and hemoglobin (Hb), lower red blood cell distribution width (RDW) than those with iron deficiency (ID) or iron overload (IO) (p < 0.05). The Hb, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) levels in gene carriers of α-thalassemia were higher than those of β-thalassemia, while RBC, RDW and serum ferritin (SF) levels were lower than the later(p < 0.05). Among individuals with -- SEA /αα, the Hb, MCV, MCH, mean corpuscular hemoglobin concentration (MCHC) and SF levels of subjects≥19 years old were higher than those of ≤18 years old. For cases ≥19 years old, the RBC, Hb and SF levels in male were higher than that in female, while MCHC level was lower than female(p < 0.05)., Conclusion: The difference of hematological phenotypes in patients with thalassemia is not only affected by their genotype, but also the influence of gender and age., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Yufang Wang reports financial support was provided by Quanzhou science and Technology Bureau., (© 2024 Published by Elsevier Ltd.)

Background: The incidence of small cell lung cancer (SCLC) among Asian patients is on the rise. Nevertheless, there remains a deficiency in precise prognostic models tailored to the specific needs of this patient population. It is imperative to develop a novel nomogram aimed at forecasting the prognosis of Asian SCLC patients., Methods: The SEER database supplied data on 661 Asian SCLC patients, who were then divided into training and internal validation sets through a random selection process. In addition, we identified 212 patients from a Chinese medical institution for the purpose of creating an external validation cohort. To forecast survival, we employed both univariate and multivariate analyses. The performance of our nomogram was assessed through calibration plots, the concordance index (C-index), and decision curve analysis (DCA)., Results: Five independent prognostic factors were determined and integrated into the nomogram. C-index values for the training and internal validation cohorts were 0.774 (95% confidence interval [CI] = 0.751-0.797) and 0.731 (95%CI = 0.690-0.772), respectively. In the external validation cohort, the C-index is 0.712 (95% CI = 0.655-0.7692). Calibration curves demonstrated highly accurate predictions. When compared to the AJCC staging system, our model exhibited improved net benefits in DCA. Furthermore, the risk stratification system effectively differentiated patients with varying survival risks., Conclusion: We have created a novel nomogram for predicting the survival of Asian patients with SCLC. This nomogram has been subjected to external validation and has shown its superiority over the conventional TNM staging system. It offers a more precise and reliable means of forecasting the prognosis of Asian SCLC patients., (© 2024 The Author(s). The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Background and Aims: Whether the natural course of ulcerative colitis (UC) in mainland China is similar or different from that in Western countries is unknown, and data on it is limited. We aimed to provide a comprehensive description of the natural course of UC in China and compare it with Western UC patients., Methods: Based on a prospective Chinese nationwide registry of consecutive patients with inflammatory bowel diseases, the medical treatments and natural history of UC were described in detail, including disease extension, surgery, and neoplasia. The Cox regression model was used to identify factors associated with poor outcomes., Results: A total of 1081 UC patients were included with a median follow-up duration of 5.3 years. The overall cumulative exposure was 99.1% to 5-aminosalicylic acids, 52.1% to corticosteroids, 25.6% to immunomodulators, and 15.4% to biologics. Disease extent at diagnosis was proctitis in 26.9%, left-sided colitis in 34.8%, and extensive colitis in 38.3%. Of 667 patients with proctitis and left-sided colitis, 380 (57.0%) experienced disease extent progression. A total of 58 (5.4%) UC patients underwent colectomy, demonstrating cumulative proportions of surgery at 1, 5, and 10 years after diagnosis of 0.6%, 3.4%, and 8.2%, respectively. In addition, 23 (2.1%) UC patients were diagnosed with neoplasia, demonstrating cumulative proportions of neoplasia at 1, 5, and 10 years after diagnosis of 0.5%, 1.0%, and 3.5%, respectively., Conclusions: Chinese UC patients had similar cumulative proportions of exposure to IBD-specific treatments but a lower surgical rate than patients in Western countries, indicating a different natural course, and close monitoring needs for UC in China. However, these results must be confirmed in population-based studies because the hospital-based cohort in our study might lead to selection bias., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

Background: The efficacy of ustekinumab (UST) and infliximab (IFX) in Crohn's disease (CD) patients with intestinal stenosis remains uncertain., Objective: This study aims to compare the efficacy of UST and IFX in the treatment of CD patients with intestinal stenosis., Design: This was a retrospective and multicenter cohort study., Methods: In this retrospective study, we included CD patients treated with IFX or UST at five centers. We assessed the clinical response rate at weeks 12 and 24, steroid-free clinical remission rate at weeks 24 and 52 for overall patients and those with stenosis, and objective examination (intestinal ultrasound and/or endoscopy) response rate at week 52 for stenosis patients., Results: A total of 211 CD patients (106 IFX and 105 UST) were included, with 119 (56 IFX and 63 UST) having intestinal stenosis. In the overall patient population, there were no significant differences in clinical response rate and steroid-free clinical remission rate at weeks 12, 24, and 52 between the IFX and UST groups. In patients with stenosis, the steroid-free clinical remission rate at week 52 was significantly lower in the IFX group compared to the UST group (51.79% IFX vs 69.84% UST, p  = 0.044). The objective examination response rate did not significantly differ between the IFX and UST groups at week 52 (66.67% IFX vs 76.19% UST, p  = 0.690). In the UST group, steroid-free clinical remission rate was higher in bio-naïve patients than bio-experienced patients at week 24 (75.00% bio-naïve vs 55.38% bio-experienced, p  = 0.043)., Conclusion: UST may be considered a more advantageous treatment option for those CD patients with intestinal stenosis, as it has better steroid-free clinical remission rates compared to IFX., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Rationale: Elderly patients with acute liver failure are highly susceptible to severe complications, such as invasive fungal infections, due to weakened immune systems and altered gut microbiota. A thorough understanding of liver failure and opportunistic infections is crucial for effective management., Patient Concerns: An 84-year-old male with acute liver failure from hepatitis E experienced worsening jaundice despite standard treatments. He also developed respiratory symptoms, including blood-streaked sputum, raising concerns about a potential fungal infection., Diagnoses: The patient was diagnosed with acute liver failure secondary to hepatitis E and an invasive fungal infection caused by Aspergillus fumigatus. Initial treatments included artificial liver plasma exchange and antifungal prophylaxis. Further diagnostics, including bronchoscopy and next-generation sequencing of alveolar lavage fluid, confirmed the Aspergillus infection., Lessons: Elderly liver failure patients are particularly prone to opportunistic infections, underscoring the need for vigilant monitoring and early intervention. Despite aggressive treatments, including antifungal therapy and artificial liver support, prognosis remains poor, highlighting the importance of prompt diagnosis and comprehensive management to enhance patient outcomes., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Plasma membrane integrity is vital not only for cell survival but also nearly all aspects of cell functioning1. Mechanical stress can cause plasma membrane damage2, but it is not known whether there are large molecules (proteins) that control plasma membrane integrity. Here we constructed a 384-well cellular stretch system that delivers precise, reproducible mechanical strain to adherent cells. Using the system, we screened 10,843 siRNAs targeting 2,726 multi-pass transmembrane proteins for stretch-induced membrane permeability changes. The screen identified NINJ1, a protein recently proposed to regulate pyroptosis and other lytic cell death 3,4 , as the top hit. We demonstrate that NINJ1 is a critical regulator for mechanical force-induced plasma membrane rupture (PMR), without the need of stimulating any cell death programs. Low NINJ1 expression renders the membrane more resistant to stretching, while high expression of NINJ1 lowers the threshold of PMR under mechanical strain. NINJ1 level on the plasma membrane is inversely correlated to tension required to rupture the membrane. In the pyroptosis context, NINJ1 on its own is not sufficient to fully rupture the membrane, and additional mechanical stress is required for full PMR. Our work establishes that NINJ1 functions as a bona fide determinant of membrane biomechanical properties. Our study also suggests that PMR across tissues of distinct mechanical environments is subjected to fine tuning by differences in NINJ1 expression and external mechanical forces., Competing Interests: Competing Interests J.B., C.P. and S.H are employees of Novartis Biomedical Research. F.S. is the scientific founder and chair of the scientific advisory board of Pyrotech Therapeutics. Other authors declare no competing final interest.

According to Levelt's language production model, to name an object, speakers must first conceptualise and lexicalise the object before its name can be articulated. Conceptualisation is conducted through the semantic network that exists at the conceptual level, with the highly activated concept(s) activating lexical items at the lemma level, that is, lexicalisation. So far, research focused mostly on semantic categories (i.e., semantic interference) but less so on animacy-a concept that is correlated with semantic categories. To investigate the role of this semantic feature in language production, we conducted a picture-word interference study in Mandarin Chinese, varying animacy congruency and controlling for classifier congruency while recording behavioural and electrophysiological responses. We observed an animacy interference effect together with a larger N400 component for animacy-incongruent versus congruent picture-word pairs, suggesting animacy-congruent concepts may be in closer proximity and hence lead to a stronger spreading of activation relative to animacy-incongruent concepts. Furthermore, a larger P600 component was observed for classifier-incongruent versus classifier-congruent picture-word pairs, suggesting syntactically driven processing of classifiers at the lemma level., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To investigate the expression of inositol polyphosphate 4-phosphatase type Ⅱ B (INPP4B) in colorectal cancer (CRC) and the relevant clinical significance, to determine the relationship between INPP4B and matrix metallopeptidase 7 (MMP7) in CRC cells, and to make preliminary exploration of the effects of INPP4B on the proliferation and migration of CRC cells and mechanisms involved., Methods: The TIMER2.0 and GEPIA2 databases were used to analyze the differences in INPP4B expression between cancer and para-cancerous tissues and the effects of such differences on the prognosis of CRC. The expression of INPP4B in 102 surgically resected CRC tumors was determined by immunohistochemistry (IHC), and the correlation between INPP4B and clinical pathological indicators was analyzed. In CRC cells with overexpressed/knocked-down INPP4B , the expression of INPP4B and MMP7 were examined by real time fluorogenic quantitative PCR, the protein expression of INPP4B was assessed by Western blot, cell proliferation was determined using the CellTiter 96® AQueous One assay, and cell migration and invasion were assessed using wound healing assay and real-time label-free dynamic cell analysis (RTCA). The LinkedOmics database was used to analyze signaling pathways related to INPP4B function, and the role of potential key molecules was validated at the cellular level., Results: Analysis with the TIMER2.0 database and GEPIA2 database showed elevated INPP4B expression (colon adenocarcinoma [COAD]: 2.30, rectal adenocarcinoma [READ]: 2.33) in CRC compared to normal tissue (COAD: 1.91, READ: 1.89). IHC testing confirmed that INPP4B was upregulated in clinical CRC tissues and paracancerous tissues ( P <0.001). Cox regression model analysis showed that INPP4B (hazards ratio [HR]=1.457, 95% confidence interval [CI]: 1.003-2.115) affected the prognosis of CRC, and the Kaplan-Meier curve showed that patients with high INPP4B expression had shorter overall survival ( P <0.05). χ 2 test was performed to analyze the relationship between INPP4B expression and clinicopathological indexes, and it was found that high expression of INPP4B was correlated with lymph node metastasis ( χ 2 =3.997, P =0.046) and neural invasion( χ 2 =8.511, P =0.004). In in vitro experiments, CRC cells overexpressing INPP4B showed a significantly increased cell proliferation and migration compared to the cells in the control group ( P <0.05). Analysis using the LinkedOmics database showed that INPP4B was correlated with extracellular matrix remodeling and cell migration. Pearson's correlation analysis showed that MMP7 was positively correlated with INPP4B ( r =0.3782, P <0.001). INPP4B overexpression or knockdown in vitro also led to the upregulation or the downregulation of MMP7 expression in CRC cells., Conclusion: INPP4B is highly expressed in CRC tissues and significantly correlated with lymph node metastasis, neural invasion, and patient prognosis. MMP7 may mediate the role of INPP4B in promoting CRC cell migration and invasion., Competing Interests: 利益冲突　本文作者王玉芳是本刊编委会编委。该文在编辑评审过程中所有流程严格按照期刊政策进行，且未经其本人经手处理。除此之外，所有作者声明不存在利益冲突。, (© 2024《四川大学学报（医学版）》编辑部 版权所有Copyright ©2024 Editorial Office of Journal of Sichuan University (Medical Sciences).)

The vaginal microbiome (VM) is associated with human papillomavirus (HPV) infection and progression, but a thorough understanding of the relation between HPV infection, and VM needs to be elucidated. From August to December 2022, women who underwent routine gynecological examinations were screened for HPV infection. The distribution of HPV variants and clinical characteristics were collected. Then, a total of 185 participants were enrolled and divided into HPV-negative (HC), high-risk HPV (H), low-risk HPV (L), multiple high-risk HPV (HH), and mixed high-low risk HPV (HL) groups. Samples were collected from the mid-vagina of these 185 participants and sent for 16S rDNA sequencing (V3-V4 region). Among 712 HPV-positive women, the top 3 most frequently detected genotypes were HPV52, HPV58, and HPV16. Among 185 participants in the microbiology study, the β diversity of the HC group was significantly different from HPV-positive groups ( P < 0.001). LEfSe analysis showed that Lactobacillus iners was a potential biomarker for H group, while Lactobacillus crispatus was for L group. Regarding HPV-positive patients, the α diversity of cervical lesion patients was remarkably lower than those with normal cervix ( P < 0.05). Differential abundance analysis showed that Lactobacillus jensenii significantly reduced in cervical lesion patients ( P < 0.001). Further community state type (CST) clustering displayed that CST IV was more common than other types in HC group ( P < 0.05), while CST I was higher than CST IV in H group ( P < 0.05). Different HPV infections had distinct vaginal microbiome features. HPV infection might lead to the imbalance of Lactobacillus spp. and cause cervical lesions., Importance: In this study, we first investigated the prevalence of different HPV genotypes in south China, which could provide more information for HPV vaccinations. Then, a total of 185 subjects were selected from HPV-negative, high-risk, low-risk, multiple hr-hr HPV infection, and mixed hr-lr HPV infection populations to explore the vaginal microbiome changes. This study displayed that HPV52, HPV58, and HPV16 were the most prevalent high-risk variants in south China. In addition, high-risk HPV infection was featured by Lactobacillus iners , while low-risk HPV infection was by Lactobacillus crispatus . Further sub-group analysis showed that Lactobacillus jensenii was significantly reduced in patients with cervical lesions. Finally, CST clustering showed that CST IV was the most common type in HC group, while CST I accounted the most in H group. In a word, this study for the first time systemically profiled vaginal microbiome of different HPV infections, which may add bricks to current knowledge on HPV infection and lay the foundation for novel treatment/prevention development., Competing Interests: W.L. and S.J. are employed by Shanghai Biotecan Pharmaceuticals Company. The other authors declare no conflict of interest.

Background: The status of the sentinel lymph nodes (SLNs) is an important prognostic factor for many different types of cancer. The one-step nucleic acid amplification (OSNA) assay has emerged as a rapid intraoperative molecular diagnostic tool for LN metastasis detection. We aimed to evaluate and summarize the value of the OSNA assay for the diagnosis of SLN metastasis in cytokeratin 19 (CK19)-positive breast cancer., Methods: To evaluate the diagnostic value, the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were pooled. The threshold effect, followed by subgroup analysis, was performed to explore the source of heterogeneity. A sensitivity analysis was performed to assess the stability of this meta-analysis model. Fagan plots and likelihood ratio scattergrams were used to explore the potential clinical significance., Results: A total of 29 eligible studies, which consisted of 5,331 patients with 10,343 SLNs, were included in this meta-analysis. The pooled sensitivity, specificity, PLR, NLR, and DOR were 0.86 (95% CI: 0.85-0.88), 0.94 (95% CI, 0.94-0.95), 18.00 (95% CI, 13.54-23.92), 0.13 (95% CI, 0.10-0.17), and 138.99 (95% CI, 86.66-222.92), respectively. The AUC was 0.97 (95% CI, 0.95-0.98). Sensitivity analysis showed that four studies had an impact on the pooled results and mainly contributed to the heterogeneity. Fagan's nomogram revealed that the prior probability was 50%, the post-probability positive was 95%, and the post-probability negative was 11%., Discussion: Our results suggested that OSNA can predict the occurrence of SLN metastasis in CK19-positive breast cancer. However, more well-designed and multicenter diagnostic tests are needed to validate our results., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Wang and Wang.)

The regulation mechanism of bamboo height growth has always been one of the hotspots in developmental biology. In the preliminary work of this project, the function of LBD transcription factor regulating height growth was firstly studied. Here, a gene PheLBD12 regulating height growth was screened. PheLBD12-overexpressing transgenic rice had shorter internodes, less bioactive gibberellic acid (GA3), and were more sensitive to GA3 than wild-type (WT) plants, which implied that PheLBD12 involve in gibberellin (GA) pathway. The transcript levels of OsGA2ox3, that encoding GAs deactivated enzyme, was significantly enhanced in PheLBD12-overexpressing transgenic rice. The transcript levels of OsAP2-39, that directly regulating the expression of EUI1 to reduce GA levels, was also significantly enhanced in PheLBD12-overexpressing transgenic rice. Expectedly, yeast one-hybrid assays, Dual-luciferase reporter assay and EMSAs suggested that PheLBD12 directly interacted with the promoter of OsGA2ox3 and OsAP2-39. Together, our results reveal that PheLBD12 regulates plant height growth by modulating GA catabolism. Through the research of this topic, it enriches the research content of LBD transcription factors and it will theoretically enrich the research content of height growth regulation., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Kinship inference has been a major issue in forensic genetics, and it remains to be solved when there is no prior hypothesis and the relationships between multiple individuals are unknown. In this study, we genotyped 91 microhaplotypes from 46 pedigree samples using massive parallel sequencing and inferred their relatedness by calculating the likelihood ratio (LR). Based on simulated and real data, different treatments were applied in the presence and absence of relatedness assumptions. The pedigree of multiple individuals was reconstructed by calculating pedigree likelihoods based on real pedigree samples. The results showed that the 91 MHs could discriminate pairs of second-degree relatives from unrelated individuals. And more highly polymorphic loci were needed to discriminate the pairs of second-degree or more distant relative from other degrees of relationship, but correct classification could be obtained by expanding the suspected relationship searched to other relationships with lower LR values. Multiple individuals with unknown relationships can be successfully reconstructed if they are closely related. Our study provides a solution for kinship inference when there are no prior assumptions, and explores the possibility of pedigree reconstruction when the relationships of multiple individuals are unknown., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Human epidermal growth factor receptor 2 (HER2) overexpression and activation are crucial for trastuzumab resistance in HER2-positive breast cancer; however, the potential regulatory mechanism of HER2 is still largely undetermined. In this study, a novel circular RNA derived from peptidylprolyl isomerase D (PPID) is identified as a negative regulator of trastuzumab resistance. Circ-PPID is highly stable and significantly downregulated in trastuzumab-resistant cells and tissues. Restoration of circ-PPID markedly enhances HER2-positive breast cell sensitivity to trastuzumab in vitro and in vivo. Circ-PPID directly binds to N-acetyltransferase 10 (NAT10) in the nucleus and blocks the interaction between NAT10 and HER2 mRNA, reducing N4-acetylcytidine (ac4C) modification on HER2 exon 25, leading to HER2 mRNA decay. Intriguingly, the subcellular localization of circ-PPID differs between trastuzumab-sensitive and -resistant cells. Circ-PPID in trastuzumab-resistant cells is located more in the cytoplasm, mainly due to the upregulation of Exportin 4 (XPO4), which results in the loss of spatial conditions for circ-PPID to bind to nuclear NAT10. Taken together, our data suggest that circ-PPID is a previously unappreciated ac4C-dependent HER2 epigenetic regulator, providing a promising therapeutic direction for overcoming trastuzumab resistance in clinical setting., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Institute of Plant Genetics Polish Academy of Sciences.)

Lung cancer accounts for the highest proportion of cancer deaths in the world and poses a great threat to human health. About 30% to 40% of non-small cell lung cancer (NSCLC) is caused by point mutations, exon insertion and exon deletion of the epidermal growth factor receptor (EGFR). In addition to the common exon 19 deletion mutation and exon 21 L858R mutation, exon 18 G719X mutation, exon 21 L861Q mutation and exon 20 S768I mutation are the most important rare mutations. At present, the diagnostic methods for major rare mutations are mainly next-generation sequencing (NGS), digital polymerase chain reaction (dPCR), droplet digital PCR (ddPCR), etc. Regarding the targeted therapy of G719X/L861Q/S768I mutant NSCLC, the first generation EGFR-tyrosine kinase inhibitors (TKIs) have poor efficacy, while the second and third generation EGFR-TKIs have similar efficacy. The novel third generation EGFR-TKIs and combination therapy show a good therapeutic prospect. This article summarized the progress in the diagnosis and targeted therapy of G719X/L861Q/S768I mutant NSCLC, so as to provide reference for subsequent clinical drug use and research.
.

DNA degradation has been a thorny problem in forensic science. Shortening the amplicon length of the genetic markers improves the analysis of degraded DNA effectively. Microhaplotype (MH) has been proposed as a potential genetic marker that can be used for degraded DNA analysis. In the present study, a 146-plex MH-next-generation sequencing (NGS) system with an average Ae of 6.876 was constructed. Unlike other MH studies, a single-primer extension (SPE)-based NGS library preparation method was used to improve the detection of MH markers for degraded DNA. SPE employs a locus-specific and universal primer to amplify target fragments, reducing the necessity for complete fragment sequences. SPE might effectively mitigate the impact of degradation on amplification. However, SPE produces amplicons of varying lengths, posing challenges in allele calling for SPE-NGS data. To address this issue, this study proposed a flexible allele-calling strategy to improve amplicon detection. In addition, this study evaluated the forensic efficacy of the system using 12 low-template samples (from 1 ng to 7.8 pg), 10 mock-degraded DNA with various degrees of degradation, and 8 forensic casework samples. When the template is as low as 7.8 pg, our system can accurately detect at least 37 loci and achieves a random match probability (RMP) of 10 -30 using the complete allele-calling strategy. Eighty-two loci can be detected, and RMP can reach 10 -54 using a flexible allele-calling strategy. After 150 min of 98°C treatment, 36 loci can still be detected, and an RMP of 10 -5 can be obtained using the flexible allele-calling strategy. Furthermore, the number of single nucleotide polymorphism detected at different DNA amounts and degradation levels suggests that the SPE method combined with a flexible allele-calling strategy is effective., (© 2024 Wiley‐VCH GmbH.)

Avian pathogenic Escherichia coli (APEC) is a widespread bacterium that causes significant economic losses to the poultry industry. APEC biofilm formation may result in chronic, persistent, and recurrent infections in clinics, making treatment challenging. Baicalein is a natural product that exhibits antimicrobial and antibiofilm activities. This study investigates the inhibitory effect of baicalein on APEC biofilm formation at different stages. The minimum inhibitory concentration (MIC) of baicalein on APEC was determined, and the growth curve of APEC biofilm formation was determined. The effects of baicalein on APEC biofilm adhesion, accumulation, and maturation were observed using optical microscopy, confocal laser scanning microscopy, and scanning electron microscopy. The biofilm inhibition rate of baicalein was calculated at different stages. The MIC of baicalein against APEC was 256 μg/mL. The process of APEC biofilm maturation takes approximately 48 h after incubation, with initial adhesion completed at 12 h, and cell accumulation finished at 24 h. Baicalein had a significant inhibitory effect on APEC biofilm formation at concentrations above 1 μg/mL (p < 0.01). Notably, baicalein had the highest rate of biofilm formation inhibition when added at the adhesion stage. Therefore, it can be concluded that baicalein is a potent inhibitor of APEC biofilm formation in vitro and acts, primarily by inhibiting cell adhesion. These findings suggests that baicalein has a potential application for inhibiting APEC biofilm formation and provides a novel approach for the prevention and control APEC-related diseases., Competing Interests: Declaration of competing interest All authors have read and approved this version of the article, and due care has been taken to ensure the integrity of the work., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To investigate the association between dietary and some other environmental factors and the risk of inflammatory bowel diseases (IBD) in Chinese population., Materials and Methods: A multicenter case-control study was conducted involving 11 hospitals across China. A total of 1,230 subjects were enrolled consecutively, and diet and environmental factor questionnaires were collected. IBD patients were matched with healthy controls (HC) using propensity-score matching (PSM) at a 1:1 ratio with a caliper value of 0.02. Multivariate conditional logistic regression analyses were performed to evaluate the associations between diet, environmental factors, and IBD., Results: Moderate alcohol and milk consumption, as well as daily intake of fresh fruit, were protective factors for both Crohn's disease (CD) and ulcerative colitis (UC). Conversely, the consumption of eggs and chocolate increased the risk of IBD. Outdoor time for more than 25% of the day was a protective factor only for CD. In eastern regions of China, CD patients had higher egg consumption and less outdoor time, while UC patients consumed more chocolate. IBD patients from urban areas or with higher per capita monthly income consumed more fruit, eggs, and chocolate., Conclusions: This study reveals an association between specific foods, outdoor time, and the emergence of IBD in the Chinese population. The findings emphasize the importance of a balanced diet, sufficient outdoor time and activities, and tailored prevention strategies considering regional variations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chu, Chen, Zhang, Wang, Guo, Chen, Liu, Zhu, He, Ding, Wang, Zheng, Cao, Yang and Qian.)

This study was aimed to evaluate the effect of vitamin E (VE) on laying performance, VE deposition, antioxidant capacity, immunity, follicle development, estrogen secretion, ovary metabolome, and cecal microbiota of laying hens. One hundred and twenty XinYang Black-Feathered laying hens (70 wk old) were randomly assigned to 2 groups (6 replicates of 20 birds), and fed a basal diet (containing 20 mg/kg VE, control (CON) group) and a basal diet supplemented with 20 mg/kg VE (VE group). The experiment lasted for 10 wk. Results showed that VE supplementation increased laying performance, antioxidant capacity, and immunity, as evidenced by increased (P < 0.05) performance (laying rate), antioxidant (glutathione peroxidase, total superoxide dismutase, total antioxidant capacity, and catalase) and immune (immunoglobulins) parameters, and decreased (P < 0.05) feed/egg ratio and malondialdehyde. Meanwhile, VE group had higher (P < 0.05) pregrade follicles, ovary index and serum estrogen levels than CON group. 16S rRNA sequencing showed that VE supplementation altered the cecal microbiota composition by increasing Bacteroides, Rikenellaceae&#95;RC9&#95;gut&#95;group, Prevotellaceae&#95;UCG-001 and Megamonas abundances and reducing Christensenellaceae&#95;R-7&#95;group abundance (at genus level), which are mainly associated with the production of short-chain fatty acids. Metabolomic profiling of the ovary revealed that the major metabolites altered by VE supplementation were mainly related to follicle development, estrogen secretion, anti-inflammatory, antioxidant, phototransduction, bile acid synthesis, and nutrient transport. Furthermore, changes in cecal microbiota (at genus level) and ovary metabolites were highly correlated with laying performance, antioxidant, and immune parameters. In summary, VE contributed to the laying performance of aged laying hens by enhancing antioxidant, immune, and ovarian functions, promoting follicle development and estrogen secretion, and regulating gut microbiota and ovary metabolites. These findings will provide a new perspective on the mechanisms of egg production in aged poultry ovaries., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Global warming can significantly impact soil CH 4 uptake in subtropical forests due to changes in soil moisture, temperature sensitivity of methane-oxidizing bacteria (MOB), and shifts in microbial communities. However, the specific effects of climate warming and the underlying mechanisms on soil CH 4 uptake at different soil depths remain poorly understood. To address this knowledge gap, we conducted a soil warming experiment (+4 °C) in a natural forest. From August 2020 to October 2021, we measured soil temperature, soil moisture, and CH 4 uptake rates at four different soil depths: 0-10 cm, 10-20 cm, 20-40 cm, and 40-60 cm. Additionally, we assessed the soil MOB community structure and pmoA gene (with qPCR) at the 0-10 and 10-20 cm depths. Our findings revealed that warming significantly enhanced soil net CH 4 uptake rate by 12.28 %, 29.51 %, and 61.05 % in the 0-10, 20-40, and 40-60 cm soil layers, respectively. The warming also led to reduced soil moisture levels, with more pronounced reductions observed at the 20-40 cm depth compared to the 0-20 cm depth. At the 0-10 cm depth, warming increased the relative abundance of upland soil cluster α (a type of MOB) and decreased the relative abundance of Methylocystis, but it did not significantly increase the pmoA gene copies. Our structural equation model analysis indicated that warming directly regulated soil CH 4 uptake rate through the decrease in soil moisture, rather than through changes in the pmoA gene and MOB community structure at the 0-20 cm depth. In summary, our results demonstrate that warming enhances soil CH 4 uptake at different depths, with soil moisture playing a crucial role in this process. Under warming conditions, the drier soil pores allow for better CH 4 penetration, thereby promoting more efficient activity of MOB., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Based on the matching of the database of China Industry Business Performance and China Customs Trade from 2000 to 2013, this paper constructs the digital product import index, and adopts the method of panel data modeling to systematically investigate the impact and mechanism of digital product import on the domestic value-added rate of Chinese enterprises' export from the theoretical and empirical aspects. The research finds that the import of digital products significantly promotes the improvement of the domestic value-added rate of enterprises' export, and the core conclusion is still valid after considering the endogeneity of variables, changing the measurement index and estimation method. The mechanism test finds that the import of digital products improves the domestic value-added rate of enterprises' export through two channels: cost markup and relative price. In addition, the heterogeneity test finds that the import of digital products has a stronger effect on the improvement of the domestic value-added rate of enterprises' export in non-export enterprises, pure general trading enterprises, foreign-funded enterprises, labor-intensive enterprises and enterprises in the eastern region., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Variations in the tumor genome can result in allelic changes compared to the reference profile of its homogenous body source on genetic markers. This brings a challenge to source identification of tumor samples, such as clinically collected pathological paraffin-embedded tissue and sections. In this study, a probabilistic model was developed for calculating likelihood ratio ( LR ) to tackle this issue, which utilizes short tandem repeat (STR) genotyping data. The core of the model is to consider tumor tissue as a mixture of normal and tumor cells and introduce the incidence of STR variants ( φ ) and the percentage of normal cells ( M xn ) as a priori parameters when performing calculations. The relationship between LR values and φ or M xn was also investigated. Analysis of tumor samples and reference blood samples from 17 colorectal cancer patients showed that all samples had Log 10 ( LR ) values greater than 10 14 . In the non-contributor test, 99.9% of the quartiles had Log 10 ( LR ) values less than 0. When the defense's hypothesis took into account the possibility that the tumor samples came from the patient's relatives, LR greater than 0 was still obtained. Furthermore, this study revealed that LR values increased with decreasing φ and increasing M xn . Finally, LR interval value was provided for each tumor sample by considering the confidence interval of M xn . The probabilistic model proposed in this paper could deal with the possibility of tumor allele variability and offers an evaluation of the strength of evidence for determining tumor origin in clinical practice and forensic identification., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hu, Zhu, Dai, Zhang, Chen, Wang, Wang, Cao, Wang and Zhang.)

Aims: The formation of anti-drug antibodies (ADAs) during anti-tumor necrosis factor (anti-TNF) therapy is reported to lead to reducing serum drug levels, which may bring about a loss of response to treatment. Previous research has suggested an association between specific antibiotic classes and ADA formation during anti-TNF therapy. However, there are few studies specifically examining this association in Chinese inflammatory bowel disease (IBD) patients. Therefore, our study aimed to evaluate the possible effect of antibiotic use on ADA formation to anti-TNF therapy in Chinese patients with IBD. Methods: A total of 166 patients with IBD, including 149 with Crohn's disease (CD) and 17 with ulcerative colitis (UC), were included in this retrospective analysis. These patients were initially treated with anti-TNF therapy (infliximab or adalimumab) after January 2018 and reviewed with available ADA levels before October 2023. After univariable analysis of all the variables, a multivariate Cox proportional hazards model was used to assess the association between antibiotic use and ADA development. Results: Among 166 IBD patients treated with infliximab (108/166, 65.1%) or adalimumab (58/166, 34.9%), 31 patients (18.7%) were measured as positive ADA levels. Cox proportional hazard model demonstrated an increased risk of ADA formation in IBD patients who used β-lactam-β-lactamase inhibitor combinations (BL-BLIs) (HR = 5.143, 95%CI 1.136-23.270, p = 0.033), or nitroimidazoles (HR = 4.635, 95%CI 1.641-13.089, p = 0.004) during 12 months before the ADA test. On the contrary, a reduced risk was noted in patients treated with fluoroquinolones (HR = 0.258, 95% CI 0.072-0.924, p = 0.037). Moreover, the median serum infliximab or adalimumab concentration in patients with positive ADA levels was significantly lower than that in patients with negative ADA levels (infliximab: 0.30 vs. 1.85 μg/mL, p < 0.0001; adalimumab: 0.45 vs. 7.55 μg/mL, p = 0.0121). Conclusion: ADA development is associated with various antibiotic classes. BL-BLIs and nitroimidazoles might increase the risk of ADA formation during anti-TNF therapy in Chinese IBD patients, while the treatment with fluoroquinolones could probably reduce such risk. There were certain limitations in the retrospective analysis of the study, therefore, the results are just for reference, and other studies are needed to further confirm our findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sun, Ju, Xu, Luo, Li and Wang.)

Inferring the number of contributors (NoC) is a crucial step in interpreting DNA mixtures, as it directly affects the accuracy of the likelihood ratio calculation and the assessment of evidence strength. However, obtaining the correct NoC in complex DNA mixtures remains challenging due to the high degree of allele sharing and dropout. This study aimed to analyze the impact of allele sharing and dropout on NoC inference in complex DNA mixtures when using microhaplotypes (MH). The effectiveness and value of highly polymorphic MH for NoC inference in complex DNA mixtures were evaluated through comparing the performance of three NoC inference methods, including maximum allele count (MAC) method, maximum likelihood estimation (MLE) method, and random forest classification (RFC) algorithm. In this study, we selected the top 100 most polymorphic MH from the Southern Han Chinese (CHS) population, and simulated over 40 million complex DNA mixture profiles with the NoC ranging from 2 to 8. These profiles involve unrelated individuals (RM type) and related pairs of individuals, including parent-offspring pairs (PO type), full-sibling pairs (FS type), and second-degree kinship pairs (SE type). Our results indicated that how the number of detected alleles in DNA mixture profiles varied with the markers' polymorphism, kinship's involvement, NoC, and dropout settings. Across different types of DNA mixtures, the MAC and MLE methods performed best in the RM type, followed by SE, FS, and PO types, while RFC models showed the best performance in the PO type, followed by RM, SE, and FS types. The recall of all three methods for NoC inference were decreased as the NoC and dropout levels increased. Furthermore, the MLE method performed better at low NoC, whereas RFC models excelled at high NoC and/or high dropout levels, regardless of the availability of a priori information about related pairs of individuals in DNA mixtures. However, the RFC models which considered the aforementioned priori information and were trained specifically on each type of DNA mixture profiles, outperformed RFC&#95;ALL model that did not consider such information. Finally, we provided recommendations for model building when applying machine learning algorithms to NoC inference., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Currently, the obvious side effects of anti-tumor drugs, premature drug release, and low tumor penetration of nanoparticles have largely reduced the therapeutic effects of chemotherapy. A drug delivery vehicle (MCN-SS-GQDs) was designed innovatively. For this, the mesoporous carbon nanoparticles (MCN) with the capabilities of superior photothermal conversion efficiency and high loading efficiency were used as the skeleton structure, and graphene quantum dots (GQDs) were gated on the mesopores via disulfide bonds. The doxorubicin (DOX) was used to evaluate the pH-, GSH-, and NIR-responsive release performances of DOX/MCN-SS-GQDs. The disulfide bonds of MCN-SS-GQDs can be ruptured under high glutathione concentration in the tumor microenvironment, inducing the responsive release of DOX and the detachment of GQDs. The local temperature of a tumor increases significantly through the photothermal conversion of double carbon materials (MCN and GQDs) under near-infrared light irradiation. Local hyperthermia can promote tumor cell apoptosis, accelerate the release of drugs, and increase the sensitivity of tumor cells to chemotherapy, thus increasing treatment effect. At the same time, the detached GQDs can take advantage of their extremely small size (5-10 nm) to penetrate deeply into tumor tissues, solving the problem of low permeability of traditional nanoparticles. By utilizing the photothermal properties of GQDs, synergistic photothermal conversion between GQDs and MCN was realized for the purpose of synergistic photothermal treatment of superficial and deep tumor tissues.

As a distinctly different way from apoptosis, ferroptosis can cause cell death through excessive accumulation of lipid peroxide (LPO) and show great potential for cancer therapy. However, efficient strategies for ferroptosis therapy are still facing great challenges, mainly due to insufficient endogenous H 2 O 2 or relatively high pH value for Fenton reaction-dependent ferroptosis, and the high redox level of tumor cells attenuates the oxidation therapy. Herein, an efficient lipid-based delivery system to load oxidation catalyst and glutathione peroxidase 4 (Gpx4) inhibitor is orchestrated, intending to amplify Fenton reaction-independent ferroptosis by bidirectional regulation of LPO accumulation. Ferric ammonium citrate (FAC), Gpx4 inhibitor sorafenib (SF), and unsaturated lipids are constructed into mPEG 2K -DSPE-modified liposomes (Lip@SF&FAC). Influenced by the high level of intratumoral glutathione, FAC can be converted into Fe 2+ , and subsequently the formed iron redox pair (Fe 2+ /Fe 3+ ) catalyzes unsaturated phospholipids of liposomes into LPO via a Fenton reaction-independent manner. Meanwhile, SF can downregulate LPO reduction by inhibiting Gpx4 activation. In vitro and in vivo antitumor experiments show that Lip@SF&FAC induces massive LPO accumulation in tumor cells and ultimately exhibits strong tumor-killing ability with negligible side effect. Consequently, this two-pronged approach provides a new ferroptosis strategy for predominant LPO accumulation and enhanced cancer therapy., (© 2023 Wiley-VCH GmbH.)

Trastuzumab notably improves the outcome of human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients, however, resistance to trastuzumab remains a major hurdle to clinical treatment. In the present study, we identify a circular RNA intimately linked to trastuzumab resistance. circ-β-TrCP, derived from the back-splicing of β-TrCP exon 7 and 13, confers trastuzumab resistance by regulating NRF2-mediated antioxidant pathway in a KEAP1-independent manner. Concretely, circ-β-TrCP encodes a novel truncated 343-amino acid peptide located in the nucleus, referred as β-TrCP-343aa, which competitively binds to NRF2, blocks SCF β-TrCP -mediated NRF2 proteasomal degradation, and this protective effect of β-TrCP-343aa on NRF2 protein requires GSK3 activity. Subsequently, the elevated NRF2 transcriptionally upregulates a cohort of antioxidant genes, giving rise to trastuzumab resistance. Moreover, the translation ability of circ-β-TrCP is inhibited by eIF3j under both basal and oxidative stress conditions, and eIF3j is transcriptionally repressed by NRF2, thus forming a positive feedback circuit between β-TrCP-343aa and NRF2, expediting trastuzumab resistance. Collectively, our data demonstrate that circ-β-TrCP-encoded β-TrCP protein isoform drives HER2-targeted therapy resistance in a NRF2-dependent manner, which provides potential therapeutic targets for overcoming trastuzumab resistance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Key Message: Transgene with recombination sites to address biosafety concerns engineered into lettuce to produce EspB and γ-intimin C280 for oral vaccination against EHEC O157:H7. Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a food-borne pathogen where ruminant farm animals, mainly bovine, serve as reservoirs. Bovine vaccination has been used to prevent disease outbreaks, and the current method relies on vaccines subcutaneously injected three times per year. Since EHEC O157:H7 colonizes mucosal surfaces, an oral vaccine that produces an IgA response could be more convenient. Here, we report on oral vaccination against EHEC O157:H7 in mice orally gavaged with transgenic lettuce that produces EHEC O157:H7 antigens EspB and γ-intimin C280. Younger leaves accumulated a higher concentration of antigens; and in unexpanded leaves of 30-day-old T2 plants, EspB and γ-intimin C280 were up to 32 and 51 μg/g fresh weight, respectively. Mice orally gavaged with lettuce powders containing < 3 µg antigens for 6 days showed a mucosal immune response with reduced colonization of EHEC O157:H7. This suggests that the transgenic lettuce has potential to be used for bovine vaccination. To promote the biosafety of crop plants producing medically relevant proteins, recombination sites were built into our transgenic lines that would permit optional marker removal by Cre-lox recombination, as well as transgene deletion in pollen by CinH-RS2 recombination. The ability to upgrade the transgenic lettuce by stacking additional antigen genes or replacing older genes with newer versions would also be possible through the combined use of Bxb-att and Cre-lox recombination systems., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In a preliminary experiment, it was found that c-myc expression was decreased following the differentiation of THP-1 cells into monocytes/macrophages induced by phorbol 12-myristate 13 acetate (PMA) + lipopolysaccharide (LPS) + interferon (IFN)-γ. The expression of miR-let-7c-5p was then found to be elevated by cross-sectional analysis using TargetScan and PubMed and differential microarray analysis. The present study aimed to investigate the role of the miR-let-7c-5p/c-myc signaling axis in the committed differentiation of THP-1 leukemic cells into monocytes/macrophages induced by PMA + LPS + IFN-γ. Human THP-1 leukemic cells were induced to differentiate into monocytes/macrophages by PMA + LPS + IFN-γ. Following induction for 48 h, the growth density of the THP-1 cells was observed directly under an inverted microscope, cell proliferation was measured using Cell Counting Kit-8 assay and the cell cycle and the expression of differentiation-related antigens (CD11b and CD14) were measured using flow cytometry. The mRNA expression of miR-let-7c-5p and c-myc was detected using reverse transcription-quantitative PCR and the protein expression of c-myc was detected using western blot analysis. Dual luciferase reporter gene analysis was used to detect the targeted binding of miR-let-7c-5p on the 3'UTR of c-myc. The relative expression of miR-let-7c-5p and c-myc genes in THP-1 cells induced by PMA + LPS + IFN-γ was found to be up- and downregulated respectively, and expression of miR-let-7c-5p was negatively correlated with the expression of c-myc gene. Dual luciferase reporter gene assays confirmed that miR-let-7c-5p targeted the 3'UTR of c-myc and inhibited luciferase activity. Following transfection with miR-let-7c-5p mimics, the expression of c-myc was markedly downregulated and the proliferative ability of the THP-1 cells was decreased, while the expression rate of CD11b and CD14 was significantly increased. The rescue experiment revealed that the effects of miR-let-7c-5p mimics on the proliferation and differentiation of THP-1 cells were attenuated by transfection with c-myc overexpression vector. Together, the findings of the present study demonstrated that miR-let-7c-5p can target the 3'UTR region of c-myc and that the miR-let-7c-5p/c-myc signaling axis is one of the critical pathways involved in the directional differentiation of leukemic cells into monocytes/macrophages., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Sun et al.)

Superhydrophobic surfaces with microstructures and multifunctionality have attracted intense research interest. Herein, a multiscale microflower structured surface (MMSS) was successfully fabricated by electrostatic air spray. To systematically study the preparation process, the influences of different electrostatic voltages, solution ratios, soaking time, spray distances, and spray time on surface morphology and hydrophobicity were analyzed. The surface has good superhydrophobic properties with a water contact angle of 162.3°, which allows the surface to be self-cleaning and antifouling. The surface hydrophobicity can be maintained after various mechanical and chemical damages. To overcome the limitation that existing droplet manipulation relies on special materials and surfaces, a new and universal droplet transport method is presented to successfully perform nondestructive droplet manipulations, which relies on external forces and droplet deformation to drive droplets. Therefore, this paper represents a different approach from previous studies of superhydrophobic surfaces and provides a new way to achieve dynamic droplet manipulations. These results indicate that the multifunctional MMSS will be widely used in industrial droplet transportation and self-cleaning applications.

Rationale: Infectious diseases, autoimmune diseases and vascular diseases can lead to intestinal ulcers, and inflammatory bowel disease is typically suspected as the underlying cause of ulcer and bleeding from the intestinal ulcers leading to bloody stool, and malnutrition. Here we report a rare case of successfully treated case of intestinal ulcer, bloody stool, and malnutrition by dietary modification and avoidance of long term barbecued spicy food and carbonated drinks., Patient Concerns: A 15-year-old male patient had repeated symptoms of blood in the stool for >10 years. Treatment for Chron's disease was not successful. An exhaustive investigation failed to confirm the diagnosis., Diagnosis Interventions: Through changing diet structure, avoiding spicy food, and supplementing enteral nutrition and recurrent glutamine., Outcomes: The patient's symptoms improved significantly, and the intestinal ulcer healed under endoscope., Lessons: Pay attention to healthy diet in life and avoid long-term consumption of spicy food and carbonated drinks., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

The human gastrointestinal tract harbors trillions of commensal microorganisms. Emerging evidence points to a possible link between intestinal fungal dysbiosis and antifungal mucosal immunity in inflammatory bowel disease, especially in Crohn's disease (CD). As a protective factor for the gut mucosa, secretory immunoglobulin A (SIgA) prevents bacteria from invading the intestinal epithelium and maintains a healthy microbiota community. In recent years, the roles of antifungal SIgA antibodies in mucosal immunity, including the regulation of intestinal immunity binding to hyphae-associated virulence factors, are becoming increasingly recognized. Here we review the current knowledge on intestinal fungal dysbiosis and antifungal mucosal immunity in healthy individuals and in patients with CD, discuss the factors governing antifungal SIgA responses in the intestinal mucosa in the latter group, and highlight potential antifungal vaccines targeting SIgA to prevent CD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sun, Ju, Xu and Wang.)

Myc is a well-known proto-oncogene that is frequently amplified and activated in breast cancer, especially in triple-negative breast cancer (TNBC). However, the role of circular RNA (circRNA) generated by Myc remains unclear. Herein, we found that circMyc (hsa&#95;circ&#95;0085533) was remarkably upregulated in TNBC tissues and cell lines, which was attributed to gene amplification. Genetic knockdown of circMyc mediated by lentiviral vector significantly inhibited TNBC cell proliferation and invasion. Importantly, circMyc increased cellular triglycerides, cholesterols and lipid droplet contents. CircMyc was detected in both cytoplasm and nucleus, cytoplasmic circMyc could directly bind to HuR protein, facilitating the binding of HuR to SREBP1 mRNA, resulting in increasing SREBP1 mRNA stability. Nuclear circMyc bound to Myc protein, facilitating the occupation of Myc on SREBP1 promoter, leading to increasing SREBP1 transcription. As a result, the elevated SREBP1 increased the expression of its downstream lipogenic enzymes, enhancing lipogenesis and TNBC progression. Moreover, the orthotopic xenograft model showed that depletion of circMyc markedly inhibited lipogenesis and reduced tumor size. Clinically, high circMyc was closely related to larger tumor volume, later clinical stage and lymph node metastasis, functioning as an adverse prognostic factor. Collectively, our findings characterize a novel Myc-derived circRNA controlling TNBC tumorigenesis via regulation of metabolic reprogramming, implying a promising therapeutic target., (© 2023. The Author(s).)

The proper assessment of DNA evidence in cases of personal identification is a recurring theme in forensics. It is common practice to evaluate the strength of DNA evidence using the likelihood ratio (LR). The accurate use of population allele frequencies is a crucial problem in LR calculation. Allele frequency differences among different populations could be estimated by the F ST values. Thus, F ST would also affect LR values by correcting the allele frequencies. In this study, Chinese population allele frequency data were selected from population reports published in Chinese and English journals. The population-specific F ST values of each population, the overall F ST values of each province, each region, and the whole country, and the locus-specific F ST values of different loci were calculated. The LRs using different allele frequencies and different F ST values were compared based on the combination of simulated genotypes. As a result, the F ST values of 94 populations, 19 provinces, 7 regions, and the whole country were obtained. The LR was overestimated using allele frequencies of the combined population containing multiple populations rather than using allele frequencies of a population, and the LRs after F ST correction were lower than those without correction. Conclusively, the correction in conjunction with corresponding F ST values can make the LRs more accurate and reasonable., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Breast cancer is the most common malignancy among women and the leading cause of cancer deaths, with complicated pathogenesis that is largely unknown. In this study, we identified a novel long non-coding RNA (lncRNA) as a critical driver of breast cancer tumorigenesis. RUNX1 intronic transcript 1 (RUNX1-IT1) was notably overexpressed in human breast cancer tissues, and knockdown of RUNX1-IT1 inhibited breast cancer cell viability and invasion, as well as tumor growth in orthotopic transplantation model. Further, RUNX1-IT1 repressed ferroptosis, a novel iron-dependent form of regulated cell death, via increasing glutathione peroxidase 4 (GPX4) expression. Specifically, RUNX1-IT1 directly bound to N6-methyladenosine m 6 A reader IGF2BP1 and promoted the formation of (insulin like growth factor 2 mRNA binding protein 1) IGF2BP1 liquid-liquid phase separation (LLPS) biomolecular condensates, resulting in more IGF2BP1 occupation on GPX4 mRNA, increasing GPX4 mRNA stability. Moreover, high RUNX1-IT1 was linked to poor prognosis, and a strong positive correlation between RUNX1-IT1 and GPX4 was observed in clinical breast cancer tissues. Taken together, our data reveal that RUNX1-IT1 promotes breast cancer carcinogenesis through blocking ferroptosis via elevating GPX4, targeting of the previously unappreciated regulatory axis of RUNX1-IT1/IGF2BP1/GPX4 may be a promising treatment for patient with breast cancer., (© 2023. The Author(s).)

The gut microbiome has been considered to play an important role in inflammatory bowel disease (IBD). Our previous study reported that tacrolimus-altered gut microbiota elicited immunoregulatory effects in both colonic mucosa and circulation, contributing to an increased allograft survival rate in mice. Here, we aimed to observe the changes in the tacrolimus-induced microbiome in a dextran sulfate sodium (DSS)-induced colitis mouse model and explore the possibility and efficacy of combination therapy with tacrolimus and the microbiome on colitis. Mice were divided into the control, DSS, tacrolimus monotherapy and tacrolimus plus Lactobacillus plantarum 550 ( Lacto )-treated groups. The body weight, stool consistency, hematochezia and survival of mice were observed daily. Total RNA from colonic mucosa was extracted and subjected to transcriptome sequencing. Cecal contents were collected and the 16S rRNA sequencing was performed to characterize the gut microbiome and the ultrahigh- performance liquid chromatography-MS/MS (UHPLC-MS/MS) was used for targeted quantification of bile acids. The results confirmed that tacrolimus significantly ameliorated DSS-induced colitis in mice. Beneficial alterations of the gut microbiome characterized by a remarkable expansion of the genus Lactobacillus were induced by tacrolimus treatment. Oral supplementation with Lacto further improved the tacrolimus-mediated suppression of body weight loss in colitis, while the survival time of mice was further prolonged and the inflammation of colonic mucosa was obviously relieved. The immune and inflammation-related signaling pathways, including IFN-γ and IFN-α response, allograft rejection, IL2 STAT5 signaling and the inflammatory response pathways, were further downregulated in the tacrolimus plus Lacto cotreatment group. Cotreatment also improved the diversity of the gut microbiome and rescued the concentration of taurochenodeoxycholic acid (TCDCA) in colitis. The latter was positively correlated with the abundance of Lactobacillus but negatively related to the disease activity index score. Overall, our results indicated that Lactobacillus plantarum promoted the therapeutic effect of tacrolimus in experimental colitis, offering a promising strategy to combine tacrolimus and Lactobacillus in the treatment of colitis patients., Competing Interests: ZL and XP are employed by Technology Research Institute of Shuxi Condiments of Sichuan Cuisine Co. LTD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lv, Zhang, He, Liu, Shao, Lv, Pu, Wang and Liu.)

Background: Escherichia coli can cause severe infections. The latter can lead to disseminated intravascular coagulation (DIC). The importance of an early diagnosis of DIC is illustrated through this case report., Aim: Review the utility and shortcomings of representative clinical indicators of E coli infection and DIC., Case Report: A 48-year-old man presented with diarrhea, nausea, and vomiting with fever of 2-day duration, during which consciousness was lost for 12 hour. Hematology was undertaken. The coagulation profile, liver function, and kidney function were determined, and blood cultures undertaken. The final diagnosis was acute gastroenteritis complicated by DIC. Meropenem (1.0 g, q8h, i.v.) was started, along with active replacement of fluids. Anticoagulant therapy (low-molecular-weight heparin 0.4 mL, q.d.s.) was given. Plasma supplementation of coagulation factors and albumin was applied. On day-5 of therapy, hematology showed the platelet count, D-dimer level, and prothrombin time to be improved significantly. Low-molecular-weight heparin treatment was stopped and antibiotic treatment was continued for 1 week. The patient made a full recovery., Conclusions: In severe infection, timely assessment of the platelet count, procalcitonin level, coagulation function, as well as rational use of antibiotics, can improve the prognosis of patients., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Traumatic brain injury (TBI) is among the most common injuries in forensic medicine, the identification of which is of particular importance in forensic practice. To reveal the circumstances and trends of TBI in the forensic field, we used the Web of Science (WoS) database for comprehensive retrieval. We made a metrological analysis of 1,089 papers in the past 50 years (1972-2021). The United States and Germany have the most forensic research on TBI. Diffuse axonal injury (DAI) has been the focus of attention for many years, and much effort has been devoted to its diagnosis in forensic pathology. Infants and children are the subgroups of most concern, especially in infant and child abuse cases. Research on identifying shaken baby syndrome has received increasing attention in recent years. Overall, our study provides a comprehensive list and analysis of the articles regarding TBI in legal medicine, which may shed light on recognizing the trends and research hotspots in this field., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Chen, Dang, Lu, Zhang, Yan, Niu, Yan and Yan.)

Millions of patients suffer from silicosis, but it remains an uncurable disease due to its unclear pathogenic mechanisms. Though the Nlrp3 inflammasome is involved in silicosis pathogenesis, inhibition of its classic downstream factors, Caspase-1 and Gsdmd, fails to block pyroptosis and cytokine release. To clarify the molecular mechanism of silicosis pathogenesis for new therapy, we examined samples from silicosis patients and genetic mouse models. We discovered an alternative pyroptotic pathway which requires cleavage of Gsdme by Caspases-3/8 in addition to Caspase-1/Gsdmd. Consistently, Gsdmd-/-Gsdme-/- mice showed markedly attenuated silicosis pathology, and Gsdmd-/-Gsdme-/- macrophages were resistant to silica-induced pyroptosis. Furthermore, we found that in addition to Caspase 1, Caspase-8 cleaved IL-1β in silicosis, explaining why Caspase-1-/- mice also suffered from silicosis. Finally, we found that inhibitors of Caspase-1, -3, -8 or an FDA approved drug, dimethyl fumarate, could dramatically alleviate silicosis pathology through blocking cleavage of Gsdmd and Gsdme. This study highlights that Caspase-1/Gsdmd and Caspase-3/8/Gsdme-dependent pyroptosis is essential for the development of silicosis, implicating new potential targets and drug for silicosis treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Kang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Although previous studies reported that gut fungal microbiota was associated with Crohn's disease (CD), only a few studies have focused on the correlation between gut fungi and clinical phenotypes of CD. Here, we aimed to analyze the association between intestinal fungi and the occurrence of CD, disease activity, biological behaviors, and perianal lesions. Stool samples from subjects meeting the inclusion and exclusion criteria were collected for running internal transcribed spacer 2 (ITS2) high-throughput sequencing. Then, correlation analysis was conducted between intestinal fungi and different clinical groups. There were 45 patients with CD and 17 healthy controls (HCs) enrolled. Results showed that two phyla, Rozellomycota and Mortierellomycota, were not present in patients with CD compared to HCs. At the same time, there was a higher abundance of fungal genera and species belonging to the phylum Ascomycota in patients with CD. SparCC network analysis showed fewer interactions among the fungal communities in patients with CD compared to HCs. Exophiala dermatitidis was positively associated with the clinical active stage and platelet count. The genus Candida was with significantly higher abundance in the non-B1 CD group based on the Montreal classification. Clonostachys, Humicola , and Lophiostoma were significantly enriched in patients with CD with perianal lesions. Our results demonstrated that the composition of the intestinal fungal microbiota in patients with CD and HCs was markedly different, some of which might play a pathogenic role in the occurrence of CD and perianal lesions. Exophiala dermatitidis and genus Candida might be associated with active disease stage and type non-B1 CD (CD with intestinal stenosis or penetrating lesions, or both), respectively., Competing Interests: The authors declare that they have no competing interests., (© 2022 Zeng et al.)

Background: This study was to investigate the prevalence of preoperative rim enhancement, and its association with clinicopathological features, relapse, and survival profiles in Chinese basal-like breast cancer (BC) patients. Materials and Methods: The preoperative breast magnetic resonance imaging images of 145 basal-like BC patients who underwent surgical excision were obtained to determine rim enhancement. Besides, based on disease status and survival status during follow-up, the 1-year relapse rate/mortality, 3-year relapse rate/mortality, 5-year relapse rate/mortality were calculated; disease-free survival (DFS) and overall survival (OS) were determined. Results: There were 51 (35.2%) patients with rim enhancement and 94 (64.8%) patients without rim enhancement. Furthermore, rim enhancement was associated with larger tumor size and advanced T stage, whereas it did not associate with age, pathological differentiation, N stage, or TNM stage. In addition, rim enhancement was associated with higher 1-, 3-, and 5-year relapse rate and shorter DFS; meanwhile, rim enhancement was associated with increased 1-, 3-, and 5-year mortality rate and decreased OS. By multivariate Cox's regression analyses, rim enhancement, pathological differentiation, and N stage independently predicted reduced DFS; T stage independently predicted declined OS. Conclusion: Preoperative rim enhancement on MRI might be a possible noninvasive indicator for guiding personalized treatment strategies and improving prognosis in Chinese basal-like BC patients.

Crohn's disease is a recurrent, progressive, immune-mediated inflammatory disease and merely manifests non-specific symptoms at early stage. In this study, we isolated peripheral blood mononuclear cells (PBMCs) to determine whether PBMC miRNAs are reliable biomarkers for Crohn's disease diagnosing and monitoring. 5 Crohn's disease patients and 5 healthy controls were recruited to find differentially expressed miRNAs by next generation sequencing. Candidate PBMC miRNAs were further validated by qRT-PCR in another cohort consisting of 86 Crohn's disease patients and 39 healthy controls. We found PBMC miR-582-5p could diagnose Crohn's disease with the area under receiver operating characteristic curve (AUROC) of 0.701(95%CI 0.606-0.796, p < .001). While PBMC miR-96-5p was significantly higher in active Crohn's disease and correlated with both clinical (ρ = 0.376, p < .001) and endoscopic activity (ρ = 0.512, p = .015). Furthermore, PBMC miR-96-5p had a better performance in recognizing active Crohn's disease with AUROC of 0.727 (95%CI 0.609-0.844, p = .001) than C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and fecal calprotectin. In conclusion, PBMC miR-582-5p may be further utilized as a diagnostic biomarker, while miR-96-5p may be a novel and valuable biomarker in monitoring disease activity., (© 2022 Federation of American Societies for Experimental Biology.)

Water-soluble tomato concentrate (WSTC), extracted from mature tomatoes, is the first health product in Europe that has been approved "to help maintain normal platelet activity to maintain healthy blood flow." We hypothesized that WSTC might exert an influence on blood flow shear stress-induced platelet aggregation (SIPA) and in turn maintains healthy blood flow. We used a microfluidic system to measure the effects of WSTC on SIPA in vitro. We also used the strenuous exercise rat model and the κ-carrageenan-induced rat tail thrombosis model to demonstrate the effects of WSTC on blood flow. WSTC significantly inhibited platelet aggregation at pathological high shear rate of 4,000 s -1 and 8,000 s -1 in vitro ( P < 0.05 or P < 0.01). WSTC reduced the platelet adhesion rate and increased the rolling speed of platelets by inhibiting binding to Von Willebrand Factor (vWF) ( P < 0.05 or P < 0.01). The oral administration of WSTC for 4 weeks in strenuous exercise rats alleviated hyper-reactivity of the platelets and led to a significant reduction in the plasma levels of catecholamine and IL-6. WSTC treatment also led to a reduction in black tail length, reduced blood flow pulse index (PI) and vascular resistance index (RI), and ameliorated local microcirculation perfusion in a rat model of thrombosis. WSTC exerted obvious inhibitory effects on the platelet aggregation induced by shear flow and alleviated the blood flow and microcirculation abnormities induced by an inflammatory reaction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Xiao, Wang, Wang, Liu, Sun, Zhang, Yin, Liao, You and Zhang.)

Background and Aims: Non-invasive biomarkers in sera of patients with inflammatory bowel disease [IBD] are not currently available for rapidly and accurately diagnosing the disease. We aimed to investigate and validate the potential roles of anti-paratuberculosis-nocardia polypeptide antibodies [anti-pTNP] in the diagnosis of IBD., Methods: Serum samples were collected from 502 patients with diagnosed Crohn's disease [CD], 141 patients with ulcerative colitis [UC], and 109 healthy donors. The levels of anti-pTNPs and anti-Saccharomyces cerevisiae antibodies [ASCAs] were determined by enzyme-linked immunosorbent assay. The effects of each variable on the diagnosis were analysed by receiver operating characteristic [ROC] analysis. We also performed an estimate study by first developing a clinical prediction model, with external validation in CD patients from nine IBD medical centres in China., Results: The levels of anti-pTNPs in sera of CD patients were higher than those in UC patients and healthy donors. The positive rates of anti-pTNPs were significantly higher in ileal CD patients than in ileocolonic and colonic CD patients, and the levels of anti-pTNP IgG in perianal patients were significantly higher than those in non-perianal CD patients. Of note, anti-pTNPs and perianal diseases were important predictors for active stage of CD patients. Discriminative ability to predict active CD patients was 0.918 (95% confidence interval [CI]:0.886-0.949)., Conclusions: Anti-pTNP functions as a novel biological marker for diagnosing CD and can be used to assess disease severity, particularly in those with lesion locations in the terminal ileum and stricturing and perianal diseases. A validated prediction model reveals that anti-pTNPs are useful for estimating the likelihood of active CD., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

HER2-positive breast cancer is an aggressive subtype of breast cancer, characterized by high malignancy and poor prognosis. Trastuzumab, the first HER2-targeted monoclonal antibody therapy, has a crucial role in a curative setting in HER2-positive breast cancer. However, frequent drug resistance inhibits its clinical efficacy. Herein, by performing circular RNA (circRNA) profiling, we identified a novel circRNA, circ-BGN, as a key contributor in trastuzumab resistance. Circ-BGN was evidently increased in trastuzumab-resistant breast cancer cells and tissues, linking to poor overall survival. Knockdown of circ-BGN inhibited breast cancer cell viability and notably restored its sensitivity to trastuzumab. Further, we found that circ-BGN could directly bind to OTUB1 and SLC7A11, enhancing OTUB1-mediated SLC7A11 deubiquitination and thereby inhibiting ferroptosis, a newly recognized form of cell death that is distinct from apoptosis, necrosis, and autophagy. Moreover, erastin, a small-molecule ferroptosis inducer, could effectively restore the anti-tumor effect of trastuzumab. Pre-clinically, the orthotopic tumor model showed that erastin significantly reduced tumor volume generated by trastuzumab-resistant breast cancer cells, which was more pronounced after combined circ-BGN knockdown. Collectively, our data reveal a novel circRNA controlling trastuzumab resistance via regulation of ferroptosis, providing a promising therapeutic strategy for trastuzumab-resistant breast cancer patients., (© 2022 Wiley Periodicals LLC.)

Background: Inflammatory bowel disease (IBD) is a complex chronic disorder characterized by systemic inflammation, which may cause abnormal state of coagulation, resulting in cardiac events. This study aimed to investigate the incidences and risks of cardiac events in patients with IBD in China., Methods: A retrospective cohort study was performed comprising 1435 patients with IBD from 12 IBD centers in China. Cases were matched with 1588 eligible participants without IBD from 12 medical centers according to age, sex, and laboratory parameters., Results: Patients with IBD in China exhibited significantly higher incidences of ischemic heart disease (IHD; coronary heart disease included) but lower frequencies of right bundle branch block and premature contraction than those of matched controls. The risk of IHD increased in patients with IBD, peaking at the age of 18-35 years. Female patients with IBD were more likely to experience IHD than male patients. The C-reactive protein (CRP) levels and neutrophil count in the peripheral blood were positively related with the risk of IHD among patients with Crohn's disease, whereas plasma fibrinogen levels were negatively related with the risk of IHD both in patients with Crohn's disease and ulcerative colitis., Conclusions: The risk of IHD is increased in patients with IBD, especially in young female patients with IBD when compared with matched non-IBD subjects. The CRP and plasma fibrinogen levels and neutrophil count in the peripheral blood may be potential predictors associated with the occurrence of IHD in patients with IBD. The study's findings have significant implications for the management and prevention of cardiac events in patients with IBD., (© The Author(s) 2021. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study investigated the use of polyurethane foam dressings to prevent local adverse reactions of subcutaneous azacitidine injection. Patients receiving a subcutaneous azacitidine injection were randomly divided into experimental and control groups. A total of 55 patients were included in each group. A polyurethane foam dressing was used to cover the injection site of patients in the experimental group. Conventional treatment was used in the control group. Injection site pain and local skin reactions were assessed after the intervention in both groups. The score and duration of pain, the incidence and duration of local skin adverse reactions, and the incidence of severe reactions in the experimental group were significantly lower than in the control group ( p  < 0.05). Polyurethane foam dressing can effectively reduce local adverse reactions of subcutaneous injection of azacitidine, relieve pain, shorten the duration of local pain and adverse reactions, and improve the quality of nursing.