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Abstract Vibrio parahaemolyticus is pathogenic to both humans and marine animals. Antimicrobial-resistant (AMR) bacteria have been reported to cause mortalities in shrimp, with phage therapy presenting an alternative and eco-friendly biocontrol strategy for controlling bacterial diseases. Therefore, this study aimed to isolate and characterize phages for their applicability in lysing Vibrio parahaemolyticus. A novel phage vB_VpaS_BP15 (BP15) belonged to the subfamily Queuovirinae with an icosahedral head measuring 69.11 ± 5.38 nm in length and 65.40 ± 6.89 nm in width, and a non-contractile sheathed tail measuring 139.81 ± 14.79 nm. The one-step growth curve indicated a latent period of 30 min and a burst size of 120 PFUs per cell. Phage BP15 exhibited tolerance to a range of temperatures and pH values. Infection dynamic curves demonstrated that BP15 was highly effective against BCRC12959 at MOIs ranging from 0.01 to 10; even at a low multiplicity of infection (MOI) of 0.001, BP15 still caused growth retention. Phage BP15 possessed a circular double-stranded DNA of 59,584 bp with a G + C content of 46.7% and lacked tRNA genes, virulence genes, and lysogeny genes. These findings highlight the promising potential of phage BP15 as a biocontrol agent against Vibrio parahaemolyticus in Taiwan.

Abstract Background The fat mass and obesity-associated protein (FTO) has been showed to be involved in the pathogenesis and progression of coronary artery disease (CAD). However, the effects of FTO variants on CAD risk remain poorly understood. We herein genotyped three SNPs (rs1121980, rs72803657, and rs4783818) in FTO to investigate the influence of FTO polymorphisms on individual susceptibility to CAD. Methods Genotyping for the three SNPs (rs1121980, rs72803657, and rs4783818) was conducted in a cohort of 712 CAD cases with 349 myocardial infarction (MI) cases and 701 control participants, utilizing the polymerase chain reaction-ligation detection reaction (PCR-LDR) technique. The associations of these SNPs with CAD were analyzed using multivariate logistic regression, and the associations with lipid profiles were assessed by the Kruskal-Wallis or Wilcoxon-Mann-Whitney tests. Results The A allele (OR = 1.26, 95% CI = 1.01–1.57, and P = 0.044) and the AA genotype (OR = 3.13, 95% CI = 1.53–6.38, and P = 0.002) of FTO rs1121980 were significantly associated with an elevated risk of CAD. Similarly, the A allele (OR = 1.54, 95% CI = 1.18–2.02, and P = 0.002) and the AA genotype (OR = 5.61, 95% CI = 2.57–12.27, and P

Abstract Background Infectious episodes contribute to morbidity and mortality in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Renal involvement, also known as ANCA-associated glomerulonephritis (AGN), is frequently observed in AAV. Little is known about whether co-infection at initial diagnosis is associated with renal outcome and prognosis in children with AGN. Methods Clinical and prognostic data for children admitted to our center with AAV from January 2001 to August 2023 were analyzed retrospectively. We compared the incidence of end-stage renal disease (ESRD) and mortality according to infection status at initial diagnosis. Results A total of 33 children with AGN were included in this study, 22 had an infection at the time of AGN diagnosis. A trend toward higher levels of proteinuria in the infected group than in the non-infected group was observed (p = 0.42). Patients in the infected group had higher creatinine and lower eGFR values than those in the non-infected group (p = 0.09). A significant decrease in HGB was observed in the infected group (p

Carbon emissions at the provincial level are mostly calculated based on production responsibility, which ignores the carbon emission accounting perspectives of consumption and income responsibility. However, scientific accounting of carbon emissions from multiple perspectives is crucial to equitably distribute the responsibilities for reducing emissions. This study utilises an input–output model for multi-regional carbon emissions to calculate carbon emissions from production-, consumption- and income-based perspectives for exploring the variability in the responsibilities for reducing emissions at the provincial level. The Tapio decoupling coefficient is used to analyse the relationship between carbon emissions and economic growth in key provinces, and the Logarithmic Mean Divisia Index (LMDI) model is used to determine the factors promoting or inhibiting the decoupling of carbon emissions under different responsibility perspectives. The results show that, firstly, the national carbon emissions illustrate the following trend: production-based emissions > income-based emissions > consumption-based emissions. Secondly, provinces in strong decoupling states are distributed in a northeast–southwest direction. Carbon emissions and decoupling situations differ among varying responsibility perspectives due to interprovincial transfers of carbon emissions. Thus, a compensation mechanism should be established to promote a fair and orderly peaking in each province. Lastly, carbon emission intensity is a factor promoting decoupling in all three perspectives. In the meantime, output scale, economic development and factor input are the major inhibiting factors for the decoupling of production-, consumption- and income-based emissions, respectively.

Abstract Background Metabolic dysfunction-associated fatty liver disease (MAFLD) is a typical hepatic steatosis with metabolic dysfunction. The composite dietary antioxidant index (CDAI) measures individual antioxidant capacity, and the relationship with MAFLD has received little attention. Our goal is to explore the association of CDAI with MAFLD. Methods Participants were selected from the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2020. CDAI was calculated basing on six dietary antioxidants, including zinc, selenium, carotenoids, and vitamins A, C, and E. Univariate regression and multivariable logistic regression analysis were conducted to evaluate the correlation between CDAI and MAFLD. We performed subgroup analysis to study the correlation in various populations. Results A total of 18,163 participants, including 13,969 MAFLD and 4,194 non-MAFLD, were included. CDAI was significantly negatively correlated with MAFLD. After adjusting for all confounders (including age, gender, race, marital status, poverty ratio, education level, drinking status, smoking status, and physical activity), individuals in the highest quartile of CDAI exhibited a 27% lower likelihood of developing MAFLD than those in the lowest quartile (OR = 0.73; 95% CI [0.66, 0.81], p

AIM: To establish an animal model of form deprivation amblyopia based on a simulated cataract intraocular lens (IOLs). METHODS: Poly(dimethyl siloxane)-SiO2 thin films (PSF) with different degrees of opacity as IOL materials were prepared. The light transmission of the PSF-IOL was measured, and its in vitro biosafety was determined by cell counting kit (CCK)-8 assay using the HLEC-B3 cell line and ARPE-19 cell line. Subsequently, the in vivo safety was determined by implanting the PSF-IOL with 10% wt SiO2 into the right eyes of New Zealand white rabbits (PSF-IOL group), and compared with two control groups: contralateral comparison group and normal control (NC) group (Contralateral comparison group: the fellow eye; NC group: a group of binocular normal rabbits without intervention). The flash visual-evoked potentials (F-VEPs) were measured to verify amblyopia. RESULTS: PSFs containing 0, 2%, and 10% wt SiO2 were successfully constructed. The 0 SiO2 PSF was transparent, while the 10% wt SiO2 PSF was completely opaque. It was found that PSF did not induce unwanted cytotoxicity in HLECs and ARPE19 cells in vitro. In vitro, PSF-IOL with 10% wt SiO2 was also non-toxic, and no significant inflammation or structural changes occurred after four weeks of PSF-IOL implantation. Finally, our IOL-simulated congenital cataract rabbit detected by F-VEPs suggested tentative amblyopia. CONCLUSION: A PSF-IOL that mimics cataracts is created. A novel form deprivation model is created by the IOL-simulated congenital cataract rabbit. It can be developed fast and stable and holds great potential for future study.

Abstract Thyroid hormones (THs) may affect chronic thyrotoxic myopathy (CTM). The relationship between TH sensitivity and CTM is inconsistent. We aimed to investigate the associations between TH sensitivity and the risk of CTM and to screen potential CTMs with strength and function tests. A total of 162 Chinese patients (36.58% men) with Graves’ disease were enrolled and divided into CTM and non-CTM groups. TH and sensitivity indices were measured. Muscle power and function were assessed by grip, upper-limb fatigue (ULFT), lower-limb fatigue (LLFT), and squat-up (SUT) tests, and walking pace. Association between sensitivity to TH indices and the risk of developing CTM was assessed via multivariate logistic regression. The diagnostic effectiveness of muscle power and function for predicting CTM was evaluated via receiver operating characteristic (ROC) curves. Thyroid feedback quantile-based index FT3 (TFQIFT3) and the parametric TFQIFT3 (PTFQIFT3), TFQIFT4, and PTFQIFT4 were positively associated with CTM risk by using inverse probability of treatment weighting multivariate logistic regression. For each 1-SD increase in TFQIFT3 and PTFQIFT3, TFQIFT4 and PTFQIFT4, the odds ratios for CTM were 1.67 (95% CI = 1.17–2.48) ,1.64 (95% CI = 1.51–2.93), 1.60 (95%CI = 1.12–2.32), 1.58 (95%CI = 1.11–2.30), respectively. LLFT and SUT best predicted male/female CTM, respectively (AUC = 0.89/0.85). In Graves’ disease patients, TH sensitivity is associated with CTM development, which can be predicted by SUT and LLFT results.

Abstract Background The World Health Organization (WHO) aims to achieve a 50% rate of exclusive breastfeeding (EBF) during the first six months of life by 2025. Continuing breastfeeding up to six months is determined by an individual woman’s choice and the availability of breastfeeding-friendly environments. Methods In this multicenter prospective longitudinal study, we identified breastfeeding-friendly environmental factors that were associated with breastfeeding practices from days 1–5 to six months postpartum. Breastfeeding-friendly environmental factors were assessed using structured questionnaires for mothers who gave birth under a Baby-Friendly Hospital Initiative (BFHI). We evaluated uptake of breastfeeding by asking mothers if they used the indicated practices, as well as their perceived level of acceptance of breastfeeding among their live-in family members and their perceived availability of lactation rooms in public settings. From 2012 to 2016, we recruited 1,870 women at 1–5 days postpartum from obstetrics medical facilities in Taiwan and followed their breastfeeding status at one, two, four, and six months postpartum. The definition of EBF was that the infant had received only breast milk since birth, with no supplemental infant formula. We categorized breastfeeding practices into two groups: continuing EBF and non-continuing EBF at six months. We used logistic regression models to identify factors associated with continuing EBF at six months postpartum. Results The prevalence of EBF and non-EBF at six months postpartum was 30.9% and 69.1%, respectively. The logistic regression analysis revealed that above university-level education, multiparity, and vaginal delivery were positively associated with continuing EBF. The Ten Step Baby-Friendly Hospital Initiative practices, perceived acceptance of breastfeeding in live-in families, and perceived availability of lactation rooms in public settings, were associated with a higher likelihood of continuing EBF. Postpartum women who returned to work at or after two months postpartum were more likely to report non-continuing EBF than women who did not return to work. Conclusion Those who promote public health should advocate for breastfeeding-friendly practices, including the adoption of breastfeeding-friendly measures in public and workplace settings and providing increased support for breastfeeding mothers during and after hospitalization.

Abstract For relaxor-ferroelectrics and relaxor-ferromagnets, the initial Ehrenfest-classification gives no phase-transition that contradicts the measured order-parameter, while the classification according to order-parameter and its derivatives raises the question about the relationships between the phase-transition and the specific-heat peak above and near the transition temperature. Here, based on the free-energy (F) of the thermodynamic limit systems when the external-field (h) tends 0, thermal equilibrium phase-transitions of thermodynamic limit systems with temperature (T) are reclassified into: (1) Discontinuous phase-transition. $$\partial F/\partial h|_{h \to 0}$$ and $$\partial F/\partial T|_{h \to 0}$$ have discontinuities in a T range; (2) Continuous phase-transition. $$\partial F/\partial h|_{h \to 0}$$ and $$\partial F/\partial T|_{h \to 0}$$ are continuous with T, while $$\partial^{2} F/\partial h\partial T|_{h \to 0}$$ and $$\partial^{2} F/\partial T^{2} |_{h \to 0}$$ have discontinuities at a T point; and (3) Diffuse phase-transition. $$\partial^{3} F/\partial h\partial^{2} T|_{h \to 0}$$ and $$\partial^{3} F/\partial T^{3} |_{h \to 0}$$ are continuous with T, while they are respectively equal to 0 at the transition-temperature (T d ) and diffuse-temperature (T s ). The diffuse-region of the phase-transition is $$T_{s} - T_{d}$$ and the diffuse-degree $$\left( {T_{s} - T_{d} } \right)/T_{d} \times {1}00\%$$ , naturally giving the relation of the phase-transition to the specific-heat peak.

Abstract Aryl thiols have proven to be a useful class of electron donors and hydrogen atom sources in photochemical processes. However, the direct activation and functionalization of C(sp2)–S bonds in aryl thiols remains elusive in the field of photochemistry. Herein, a photochemical carboxylation of C(sp2)–S bonds in aryl thiols with CO2 is reported, providing a synthetic route to important aryl carboxylic acids. Moreover, different kinds of aryl thiol derivatives, benzeneselenol and diphenyl diselenide also show moderate-to-high reactivity in this transformation. Mechanistic studies, including DFT calculations, suggest that the in situ generated carbon dioxide radical anion (CO2 •−) and disulfide might be the key intermediates, which undergo radical substitution to yield products. This reaction features mild and catalyst-free conditions, good functional group tolerance and wide substrate scope. Furthermore, the efficient degradation of polyphenylene sulfide highlights the usefulness of this methodology.

Abstract HER2 antagonists remain the cornerstone of therapy for patients with HER2-positive breast cancer. This study introduces a novel small-molecule inhibitor of DNA methyltransferase 1 (DNMT-1), referred to as DI-1, designed to synergize with HER2 antagonists in treating HER2-positive breast cancer cells. Clinical data reveal a negative correlation between DNMT-1 expression and PTEN levels, and a positive correlation with the methylation rates of PTEN's promoter. In experiments with SKBR3 and BT474 cells, DI-1 effectively reduced the methylation of PTEN's promoter region, thereby upregulating PTEN expression. This upregulation, in turn, enhanced the cells' sensitivity to HER2 antagonists, indicating that DI-1’s mechanism involves inhibiting DNMT-1’s recruitment to PTEN's promoter region. Consequently, by increasing PTEN expression, DI-1 amplifies the sensitivity of HER2-positive breast cancer cells to treatment, suggesting its potential as a promising therapeutic strategy in this context.

Abstract Objective The aim of our study was to evaluate the indocyanine green (ICG) retention test as a noninvasive marker of esophageal varices(EV). Methods The clinical data of patients diagnosed with compensated liver cirrhosis in Tianjin Second People’s Hospital between January 2018 and January 2021 were analysed with SPSS 23.0. Result A total of 144 patients (88 M/56 F, 51.7 ± 11.06 years) were enrolled. The ICG retention at 15 min(ICG-r15), PVD, TBIL, Cholinesterase(CHE), AST to ALT ratio(ARR), APRI, splenic area, Lok index, Park index and liver stiffness measurement in the absent or small EV group were lower than those in the medium or large EV group, while the ICG disappareance rate(ICG-K), Effective hepatic blood flow(EHBF), ALB, PLT, and Platelet to Spleen Diameter Ratio(PSDR) were higher, and the differences were significant (P

Abstract Septic acute kidney injury (AKI) is a fatal disease in the intensive care unit, with ferroptosis playing a crucial role in its pathogenesis. Long non‐coding RNA (LncRNA) metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) has been implicated in septic‐induced AKI inflammation and apoptosis. However, its regulatory role in ferroptosis and underlying mechanisms remain unclear. In vivo and in vitro models of septic AKI were established using cecal ligation and puncture (CLP) and lipopolysaccharide (LPS) challenge, respectively. Serum levels of creatinine (Cr), blood urea nitrogen (BUN), kidney injury molecule‐1 (Kim‐1), neutrophil gelatinase‐associated lipocalin (NGAL), and inflammatory cytokine in kidney tissues were determined by ELISA kits. Histopathological alterations and apoptosis were evaluated by HE staining and TUNEL. Ferroptosis was accessed by measuring MDA, GSH, Fe2+, total and lipid ROS levels, and mitochondrial ultrastructure changes. Target molecular levels were determined using RT‐qPCR, Western blotting, and immunofluorescence. Interactions among MALAT1, acyl‐CoA synthetase family member 2 (ACSF2) and FUS RNA binding protein (FUS) were validated by RIP and RNA‐pull down. MALAT1 level was significantly elevated in both in vivo and in vitro septic AKI models, of which knockdown impeded ferroptosis to alleviate septic AKI. Mechanistically, high MALAT1 expression increased ACSF2 mRNA stability via interaction with FUS. Rescue experiments showed that ACSF2 overexpression partially reversed the ferroptosis inhibition mediated by MALAT1 silencing. MALAT1 induces ferroptosis and exacerbates septic AKI by stabilizing ACSF2 mRNA with the assistance of FUS. These findings provide theoretical evidence for MALAT1 as a potential therapeutic target for septic AKI.

Abstract Background Post-stroke cognitive impairment (PSCI) not only increases patient mortality and disability, but also adversely affects motor function and the ability to perform routine daily activities. Current therapeutic approaches for, PSCI lack specificity, primarily relying on and medication and traditional cognitive therapy supplemented by a limited array of tools. Both transcranial direct current stimulation (tDCS) and virtual reality (VR) training have demonstrated efficacy in improving cognitive performance among PSCI patients. Previous findings across various conditions suggest that implementing a therapeutic protocol combining tDCS and VR (tDCS - VR) may yield superior in isolation. Despite this, to our knowledge, no clinical investigation combining tDCS and VR for PSCI rehabilitation has been conducted. Thus, the purpose of this study is to explore the effects of tDCS - VR on PSCI rehabilitation. Methods This 4-week, single-center randomized clinical trial protocol will recruit 200 patients who were randomly assigned to one of four groups: Group A (tDCS + VR), Group B (tDCS + sham VR), Group C (sham tDCS + VR), Group D (sham tDCS + sham VR). All four groups will receive conventional cognitive rehabilitation training. The primary outcome measurement utilizes the Mini-Mental State Examination (MMSE). Secondary outcome measures include the Montreal Cognitive Assessment, Frontal Assessment Battery, Clock Drawing Test, Digital Span Test, Logic Memory Test, and Modified Barthel Index. Additionally, S-YYZ-01 apparatus for diagnosis and treating language disorders assesses subjects’ speech function. Pre- and post-four-week intervention assessments are conducted for all outcome measures. Functional near-infrared spectroscopy (fNIRS) is employed to observe changes in oxygenated hemoglobin (HbO), deoxy-hemoglobin (HbR), and total hemoglobin (HbT) in the cerebral cortex. Discussion Our hypothesis posits that the tDCS - VR therapy, in opposed to individual tDCS or VR interventions, could enhance cognitive function, speech ability and daily living skills in PSCI patients while concurrently augmenting frontal cortical activity. This randomized study aims to provide a robust theoretical foundation supported by scientific evidence for the practical implementation of the tDCS - VR combination as a secure and efficient PSCI rehabilitation approach. Trial registration Chictr.org.cn Identifier: ChiCTR2300070580. Registered on 17th April 2023.

Abstract The purpose of this study is to develop a nomogram model for early prediction of the severe mycoplasma pneumoniae pneumonia (SMPP) in Pediatric and Adult Patients. A retrospective analysis was conducted on patients with MPP, classifying them into SMPP and non-severe MPP (NSMPP) groups. A total of 550 patients (NSMPP 374 and SMPP 176) were enrolled in the study and allocated to training, validation cohorts. 278 patients (NSMPP 224 and SMPP 54) were retrospectively collected from two institutions and allocated to testing cohort. The risk factors for SMPP were identified using univariate analysis. For radiomic feature selection, Spearman’s correlation and the least absolute shrinkage and selection operator (LASSO) were utilized. Logistic regression was used to build different models, including clinical, imaging, radiomics, and integrated models (combining clinical, imaging, and radiomics features selected). The model’s discrimination was evaluated using a receiver operating characteristic curve, its calibration with a calibration curve, and the results were visualized using the Hosmer–Lemeshow goodness-of-fit test. Thirteen clinical features and fourteen imaging features were selected for constructing the clinical and imaging models. Simultaneously, a set of twenty-five radiomics features were utilized to build the radiomics model. The integrated model demonstrated good calibration and discrimination in the training cohorts (AUC, 0.922; 95% CI: 0.900, 0.942), validation cohorts (AUC, 0.879; 95% CI: 0.806, 0.920), and testing cohorts (AUC, 0.877; 95% CI: 0.836, 0.916). The discriminatory and predictive efficacy of the clinical model in testing cohorts increased further after clinical and radiological features were incorporated (AUC, 0.849 vs. 0.922, P = 0.002). The model demonstrated exemplary predictive efficacy for SMPP by leveraging a comprehensive set of inputs, encompassing clinical data, quantitative and qualitative radiological features, along with radiomics features. The integration of these three aspects in the predictive model further enhanced the performance of the clinical model, indicating the potential for extensive clinical applications.

Abstract Background The aim of this study is to assess the feasibility and safety of monitored anesthesia care (MAC) versus intubated general anesthesia (IGA) for patients undergoing elective cardiac surgery with cardiopulmonary bypass (CPB). Methods This prospective observational study included patients scheduled for cardiac surgery involving CPB at our institution between April 2012 and February 2017. The enrolled patients were categorized into MAC and IGA groups. MAC involved local anesthesia at the sternotomy site, sedation with dexmedetomidine, analgesia with remifentanil/sufentanil, and electroacupuncture (EA). Eleven patients underwent MAC, and 13 patients received IGA. There were no instances of conversion from MAC to IGA, and both groups exhibited no major complications. The demographic characteristics, baseline parameters, and operative variables were comparable between the two groups. Results Intraoperative opioid consumption was significantly lower in the MAC group compared to the IGA group (P

Abstract Ovarian cancer is the fifth most prevalent cancer in women. Chemotherapy is a major treatment option for patients with advanced ovarian cancer (OC). Quinoline-2-thione and its derivatives are potential candidates for tumor therapy. In this study, we investigated the anticancer activity of the quinoline-2-thione derivative KA3D against ovarian cancer. The effect of KA3D on the viability of ovarian cancer cells was evaluated using MTT assay, and its effects on apoptosis and the cell cycle were detected using flow cytometry. Western blotting was performed to identify apoptosis-and cell cycle-related proteins altered by KA3D treatment. A xenograft model was used to verify the inhibitory effect of KA3D in vivo. H&E staining, biochemical indicator detection, and blood cell counts were used to observe the toxicity and side effects of KA3D. KA3D treatment impeded cell viability, induced apoptosis, and impeded the G2 phase of the cell cycle in ovarian cancer cells. Mechanistically, we found that KA3D enhanced the expression of proapoptotic molecules such as BAX and Caspase 3, while antiapoptotic proteins such as BCL2 were inhibited. The G0/G1 phase-related protein cyclin D1 was reduced and the G2 phase-related protein cyclin B1 was upregulated. In vivo, KA3D displayed potent anticancer activity, with no apparent toxicity in BABLC/c nude mice bearing SKOV3 cells. KA3D demonstrated remarkable chemotherapeutic drug efficacy in terms of significant cancer suppression in vitro and in vivo with low toxicity.

Autoimmune diseases result from the immune system’s response to autoantigen components, leading to damage to one’s own tissues and organs. The correlation between long noncoding RNAs (lncRNAs) and autoimmune diseases remains inconclusive. However, recent studies have revealed that the lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) plays a vital role in the development of various autoimmune diseases. Here, this review briefly summarizes the progress in understanding NEAT1 expression variations and related mechanisms in different autoimmune diseases, and discusses its potential use for future therapeutic applications.

Abstract During the oilfield development process, various factors can cause different types of reservoir damage, leading to reduced oil well production or even shutdown, and decreased water injection capacity in water wells, resulting in significant economic losses for the oilfield. However, formation damage control measures must be based on the quantitative diagnosis of the types and degrees of reservoir damage. This paper establishes a spatiotemporal evolution numerical model for 12 common types of damage during the oil and gas exploration and development process, based on the material balance theory and Fick’s diffusion law in reservoir damage processes. This model achieves numerical simulation of the degree of various reservoir damage types in different spatiotemporal domains. The overall damage degree of a specific well’s evolution with time and space is further simulated in simple superposition way. The sequential core flow experiment was carried out in the laboratory, and then compared with the calculation results. The accuracy is above 90%. Finally, using field test data, the simulation results show a 95% or higher degree of agreement with the actual field measurements, proving that the reservoir damage spatiotemporal evolution quantitative simulation technology established in this paper has high accuracy and practicality.

Abstract Background Treating mitochondrial dysfunction is a promising approach for the treatment of post-stroke cognitive impairment (PSCI). HuMSC-derived exosomes (H-Ex) have shown powerful therapeutic effects in improving mitochondrial function, but the specific effects are unclear and its brain tissue targeting needs to be further optimized. Results In this study, we found that H-Ex can improve mitochondrial dysfunction of neurons and significantly enhance the cognitive behavior performance of MCAO mice in OGD/R-induced SHSY5Y cells and MCAO mouse models. Based on this, we have developed an exosome delivery system loaded with superparamagnetic iron oxide nanoparticles (Spion-Ex) that can effectively penetrate the blood-brain barrier (BBB). The research results showed that under magnetic attraction, Spion-Ex can more effectively target the brain tissue and significantly improve mitochondrial function of neurons after stroke. Meanwhile, we further confirmed that miR-1228-5p is a key factor for H-Ex to improve mitochondrial function and cognitive behavior both in vivo and in vitro. The specific mechanism is that the increase of miR-1228-5p mediated by H-Ex can inhibit the expression of TRAF6 and activate the TRAF6-NADPH oxidase 1 (NOX1) pathway, thereby exerting protective effects against oxidative damage. More importantly, we found that under magnetic attraction, Spion-Ex exhibited excellent cognitive improvement effects by delivering miR-1228-5p. Conclusions Our research found that H-Ex has a good therapeutic effect on PSCI by increasing the expression of miR-1228-5p in PSCI, while H-Ex loaded with Spion-Ex exhibited more excellent effects on improving mitochondrial function and cognitive impairment under magnetic attraction, which can be used as a novel strategy for the treatment of PSCI.

Abstract Ferroptosis is a novel form of programmed cell death caused by damage to lipid membranes due to the accumulation of lipid peroxides in response to various stimuli, such as high levels of iron, oxidative stress, metabolic disturbance, etc. Sugar, lipid, amino acid, and iron metabolism are crucial in regulating ferroptosis. The solute carrier transporters (SLCs) family, known as the “metabolic gating” of cells, is responsible for transporting intracellular nutrients and metabolites. Recent studies have highlighted the significant role of SLCs family members in ferroptosis by controlling the transport of various nutrients. Here, we summarized the function and mechanism of SLCs in ferroptosis regulated by ion, metabolic control of nutrients, and multiple signaling pathways, with a focus on SLC–related transporters that primarily transport five significant components: glucose, amino acid, lipid, trace metal ion, and other ion. Furthermore, the potential clinical applications of targeting SLCs with ferroptosis inducers for various diseases, including tumors, are discussed. Overall, this paper delves into the novel roles of the SLCs family in ferroptosis, aiming to enhance our understanding of the regulatory mechanisms of ferroptosis and identify new therapeutic targets for clinical applications.

Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because in the early stages it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay.

Abstract Background Liver cancer (LC) screening, such as AFP test and abdominal ultrasound, is an effective way to prevent LC, one of the most common cancers worldwide. Despite the proven screening benefits, screening participation among high-risk populations for LC remains low. This suggests that targeted, systematic, and effective interventions should be provided to improve knowledge and awareness related to LC screening, enhance screening intentions, and thereby promote screening behaviors. Telephone is people’s main medium of daily communication and mHealth-based programs offer a potential and effective solution for promoting health behaviors. The purpose of this study is to develop and implement a mHealth (WeChat app) based intervention guided by Fogg’s Behavior Model (FBM) to augment the knowledge of LC prevention among people at risk of LC and enhance their motivation for screening, and to validate its effectiveness in improving LC screening. Methods We propose a two-arm, single-blind randomized controlled trial with 82 at-risk individuals of LC, delivering a 6-month mHealth-based intervention program with optional health counseling. Recruitment will be through tertiary hospitals and community organizations in 4 districts in Heng Yang. In total, 82 individuals at high risk for HCC will be randomized 1:1 to intervention or control (usual care) groups. The intervention group will receive intervention, whose contents are based on the FBM model, via multiple forms of media including PowerPoint presentation, multimedia video, health information booklet and screening message, which is delivered in the WeChat Applet. Control dyads will be provided with usual health education. Outcomes will be assessed at baseline and post-intervention. Discussion The findings of this study will provide evidence of the benefits of utilizing mHealth-based approaches in intervention development to enhance the effectiveness of screening adherence for high-risk people of LC. Further, the findings would provide reference to the potential incorporation of the targeted intervention in local community organizations. Trial registration Chinese Clinical Trial Registry (ChiCTR2400080530) Date registered: 31/1/2024.

Abstract To report the correlation between corneal biomechanical parameters and age in healthy Chinese individuals. This cross-sectional study was conducted on 864 eyes of 543 healthy participants. A comprehensive ophthalmic examination and corneal biomechanics examination using Corneal Visualization Scheimpflug Technology (Corvis ST) were conducted. Based on age, all participants were further divided into five age groups (n) as follows: group A, 11–20 years (105); group B, 21–30 years (112); group C, 31–40 years (113); group D, 41–50 years (100); and group E, > 50 years (113). Using Corvis ST, we examined 35 corneal biomechanical parameters and compared them across the different age groups. Spearman’s correlation coefficients and stepwise multivariate linear regression models were used to investigate whether the corneal biomechanical parameters were related to demographic and ocular characteristics. A correlation analysis between the left and right eyes revealed that 13 parameters were significantly associated with eye differences. Among the 35 corneal biomechanical parameters, 28 exhibited significant differences across the age groups, with stiffness parameter at applanation 1(SPA1) showing an upward trend after the age of 30 and stress–strain index (SSI) demonstrates a statistically significant upward trend when comparing the five age groups in the study. Additionally, Spearman’s correlation analysis and stepwise multivariate linear regression analysis revealed that 11 corneal biomechanical parameters were positively correlated with age and 10 were negatively correlated with age. Corvis biomechanical index (CBI) was significantly negatively correlated with intraocular pressure (IOP) and central corneal thickness (CCT), SSI was significantly positively correlated with age and IOP, and SPA1 were positively correlated with IOP and CCT. In conclusion, most corneal biomechanical parameters showed a significant correlation with age, with corneal stiffness progressively increasing alongside advancing age, IOP, or CCT.

Abstract In a multicenter case–control investigation, we assessed the efficacy of the Electrooculogram Signal Analysis (EOG-SA) method, which integrates attention-related visual evocation, electrooculography, and nonlinear analysis, for distinguishing between intellectual and developmental disabilities (IDD) and typical development (TD) in children. Analyzing 127 participants (63 IDD, 64 TD), we applied nonlinear dynamics for feature extraction. Results indicated EOG-SA’s capability to distinguish IDD, with higher template thresholds and Correlation Dimension values correlating with clinical severity. The template threshold proved a robust indicator, with higher values denoting severe IDD. Discriminative metrics showed areas under the curve of 0.91 (template threshold) and 0.85/0.91 (D2), with sensitivities and specificities of 77.6%/95.9% and 93.5%/71.0%, respectively. EOG-SA emerges as a promising tool, offering interpretable neural biomarkers for early and nuanced diagnosis of IDD.

Abstract Ferritin, comprising heavy (FTH1) and light (FTL) chains, is the main iron storage protein, and pancreatic cancer patients exhibit elevated serum ferritin levels. Specifically, higher ferritin levels are correlated with poorer pancreatic ductal adenocarcinoma (PDAC) prognosis; however, the underlying mechanism and metabolic programming of ferritin involved in KRAS-mutant PDAC progression remain unclear. Here, we observed a direct correlation between FTH1 expression and cell viability and clonogenicity in KRAS-mutant PDAC cell lines as well as with in vivo tumor growth through the control of proline metabolism. Our investigation highlights the intricate relationship between FTH1 and pyrroline-5-carboxylate reductase 1 (PYCR1), a crucial mitochondrial enzyme facilitating the glutamate-to-proline conversion, underscoring its impact on proline metabolic imbalance in KRAS-mutant PDAC. This regulation is further reversed by miR-5000-3p, whose dysregulation results in the disruption of proline metabolism, thereby accentuating the progression of KRAS-mutant PDAC. Additionally, our study demonstrated that deferasirox, an oral iron chelator, significantly diminishes cell viability and tumor growth in KRAS-mutant PDAC by targeting FTH1-mediated pathways and altering the PYCR1/PRODH expression ratio. These findings underscore the novel role of FTH1 in proline metabolism and its potential as a target for PDAC therapy development.

Background: Endocervical adenocarcinoma (ECA) comprises a heterogeneous group of diseases whose incidence has increased significantly in recent decades. ECA can be histologically classified into human papillomavirus-associated (HPVA) and non-HPVA (NHPVA) types. Given the variability in pathological features and clinical behavior between the subtypes, evaluating their respective immune microenvironments is essential. They can be categorized into distinct tumor microenvironment immune types (TMIT). Methods: A total of 540 surgically resected ECA samples were classified into HPVA and NHPVA subgroups. Tumor-infiltrating immune markers were assessed using immunohistochemistry. We categorized ECA into four TMIT based on PD-L1 and CD8+ tumor-infiltrating lymphocytes (TILs) expression, and analyzed their prognostic significance. Results: PD-L1 positivity was observed in 319 out of 464 (68.8%) HPVA and 55 out of 76 (72.4%) NHPVA. Across the entire cohort, high CD8+ TILs expression was significantly associated with improved disease-free survival (DFS, p=0.018) and overall survival (OS, p=0.031). A total of 177 samples (32.8%) were classified as TMIT I (high PD-L1 and high CD8+ TILs), exhibiting markedly denser immune cell infiltration compared to the other TMIT groups. In NHPVA subgroup, TMIT was significantly associated with both DFS (p=0.005) and OS (p=0.003). Multivariate analysis identified TMIT as an independent prognostic factor for DFS in the NHPVA group, with TMIT I indicating a more favorable prognosis (p=0.042). Conclusions: TMIT I group within the NHPVA population is most likely to benefit from PD-L1/PD-1 blockade immunotherapies. The immune classification of ECA demonstrates significant prognostic value, suggesting its potential utility in guiding clinical stratification and therapeutic decision-making.

IntroductionImmune inflammatory response plays an important role in chronic obstructive pulmonary disease (COPD). However, the cellular immune status of patients with COPD at different phases is unclear. Herein, we aim to investigate the distribution and functional status of T cell subsets in different phases of COPD (acute exacerbation of COPD [AECOPD] and stable COPD [SCOPD]).MethodsThis is an observational case-control study undertaken in West China Hospital. The distribution of T cell subsets in peripheral blood of AECOPD, SCOPD, and healthy controls (HCs) was measured using multi-color flow cytometry, and the functional status was analyzed by additional staining of activation markers.ResultsA total of 43 HCs, 43 SCOPD patients, and 64 AECOPD patients were evaluated. The total number and percentage of lymphocytes and the CD4+/CD8+ T cells ratio were significantly lower in AECOPD patients when compared to HCs. HLA-DR expression in CD3+, CD4+, CD8+, CD8+ TCR aβ, and CD4+ TCR aβ T cells was upregulated in the AECOPD group. Similarly, the expressions of HLA-DR, CD57, and PD-1 were higher in T cell subsets in the AECOPD group. Compared with the SCOPD and HC groups, the AECOPD had a significantly lower proportion of CD4+CD27+CD28+ T cells, but opposite results were found for CD4+CD27-CD28- T cells. In addition, the proportion of CD4+CD39+ T cells and CD4+CD25+FoxP3+ T cells was significantly higher in the AECOPD and SCOPD groups when compared to the HC group (P < 0.05).DiscussionThe distribution of nearly half the T cell subsets in AECOPD patients was significantly different from that in SCOPD patients and HCs. AECOPD patients may have cellular immune suppression, immune dysfunction, abnormal activation, and higher senescence depletion of T cells.

Although numerous studies have independently tested the roles of physiological integration and parental effects on the performance of clonal plant species, few have assessed them simultaneously. Moreover, the capacity for physiological integration differs greatly within species of clonal plants. We conducted a greenhouse experiment with eight genotypes of the clonal herb Hydrocotyle verticillata. In the first phase, we either severed or maintained the connections between the original proximal nodes (the basal portion) and the new distal nodes (the apical portion) of each genotype. In the second phase, the ramets in the apical portion produced in the first phase were selected and cultivated, and their connections were subjected to the same severance treatments. In the first phase, the negative effects of severance on the apical portion balanced the positive effects of severance on the basal portion, resulting in no net effect of severance on total mass, leaf mass, stem mass, and ramet number for the whole clone. In the second phase, the effects of parental severance on stem mass of the apical portion of H. verticillata varied among the eight genotypes. Additionally, the positive effect of physiological integration on offspring generations was greater in the apical portion and the whole clone of one genotype when the parental connections were intact than when they were severed, whereas it was greater in the apical portion of another genotype when the parental connections were severed than when they were intact. Our results suggest that clonal parental effects can influence the capacity for physiological integration of offspring generations and that these effects may differ among genotypes within a species.

Objective: We aimed to investigate the effects of Tongluo Zhitong formula on synovial fibroblast proliferation in human knee osteoarthritis (KOA). Methods: Discarded synovial tissue collected from patients undergoing total knee arthroplasty at our hospital was digested with type I collagenase. Primary culture was performed on three to four generations of fibroblasts, which were treated with high, medium, and low concentrations of Tongluo Zhitong formula. The KOA synoviocyte proliferation level was detected through applying the methyl-thiazol-tetrazolium (MTT) method, and cell morphology at each concentration was observed under inverted microscopy. Results: Significant differences were observed between three concentration categories and a blank control (p 0.05). The proportion of cells in the mitotic preparation phase significantly increased in the high and medium concentration categories (p

Soil salinization poses a significant ecological and environmental challenge both in China and across the globe. Plant growth-promoting rhizobacteria (PGPR) enhance plants’ resilience against biotic and abiotic stresses, thereby playing a vital role in soil improvement and vegetation restoration efforts. PGPR assist plants in thriving under salt stress by modifying plant physiology, enhancing nutrient absorption, and synthesizing plant hormones. However, the mechanisms through which PGPR regulate the contents of carbon (C) and nitrogen (N), and biomass allocation of desert plant in response to salt stress is still unclear. This study explores the impact of PGPR on biomass allocation, C, and N contents of R. soongorica seedlings through a pot experiment. Strains P6, N20, and N21, identified as Enterobacter, were isolated from the rhizosphere of R. soongorica, and they exhibited various beneficial traits such as indole-3-acetic acid (IAA) production, phosphate solubilization, nitrogen fixation, and tolerance to up to 8% NaCl stress. We found that under NaCl stress, R. soongorica seedlings exhibit significant reductions in plant height, basal diameter, and root surface area (P

Due to the codon bias of different species, codon optimization is usually carried out in the process of heterologous protein expression. At present, there are a variety of codon optimization tools. However, the optimized sequences may still have high or low points of local guanine and cytosine (GC) content, which is not conducive to the primer design of gene subcloning, and also makes it difficult to perform the experiment of synthesizing the whole gene with DNA fragments by polymerase chain reaction (PCR) reaction. In this study, we present a stand-alone software written in Python, with which users can manually check and adjust the GC content of sequence-optimized genes. The software takes the codon frequency of Escherichia coli as default and can work with other species as well. It provides a Graphical User Interface (GUI) interface, which allows users to change codons and intuitively see the effect of codon changes on local GC content. Our program brings convenience for the optimization of gene GC content and the subsequent gene cloning experiments.

BackgroundTicks are widely distributed throughout China and are the second most prevalent pathogen vectors in the world, following only mosquitoes. Tick bites can lead to Lyme disease, forest encephalitis, and other illnesses that may result in death under severe circumstances. Materials and methods: Ticks collected from March 2021 to May 2023 were pooled and used in metatranscriptomic analyses to gain insight into the diversity and distribution of tick-borne viruses in Inner Mongolia. Next-generation sequencing (NGS) outcomes were validated, and viral prevalence across distinct tick species was determined through the application of polymerase chain reaction (PCR) paired with Sanger sequencing.ResultsA total of 20 RNA viruses belonging to at least 8 families, including Chuviridae, Flaviviridae, Solemoviridae, Nairoviridae, Partitiviridae, Phenuiviridae, Rhabdoviridae, and Totiviridae, and to unclassified families were identified by NGS. Five of the identified RNA viruses (Nuomin virus, Yezo virus, tick-borne encephalitis virus, Alongshan virus, and Beiji nairovirus) are considered human pathogens. A potential human pathogen, Mukawa virus, was also among the identified viruses. Ixodes persulcatus carried a significantly greater number of viral species than did Dermacentor nuttalli, Hyalomma marginatum, and Haemaphysalis concinna. The prevalence of coinfection with multiple viruses differed in I. persulcatus from Hinggan League and Hulun Buir, and Beiji nairovirus was the codominant virus species.ConclusionsThere is a remarkable diversity of RNA viruses harboured by ticks in Inner Mongolia, with variations observed in the distribution of these tick-borne viruses across different regions and tick hosts.

To report a novel variation in the TRIM8 gene in a Chinese patient who developed focal segmental glomerulosclerosis (FSGS) and neurogenic bladder. Retrospective analysis of the clinical manifestations, laboratory results, renal biopsy results, and genetic data of the patient with FSGS complicated with neurogenic bladder. The patient was a 6-year and 8-month-old Chinese Zang ethnic boy with low-set ears, widely-spaced eyes (inner canthal distance exceeds the 95th percentile of normal inner canthal distance), a small jaw, and a short neck. He could not walk and speak complete sentences until age of 2 years. At age of 4 years, the boy was noticed to have daytime urinary incontinence, hesitancy, and urgency. Combined with urodynamic examination and magnetic resonance imaging examination results, the patient was diagnosed with a neurogenic bladder. Proteinuria was also found. The levels of uric acid, serum creatinine, and blood urea nitrogen were increased. Vitamin D deficiency, hypokalemia, hypocalcium, and hypophosphorus were detected. Urinary ultrasound showed shrinkage of both kidneys. After hospital admission, he was diagnosed with FSGS and stage 3b chronic kidney disease (CKD). Eight months after the first diagnosis, the disease progressed to stage 5 CKD. Gene analysis using whole-exome capture and sequencing revealed a de novo heterozygous pathogenic variation in the TRIM8 gene [NM_030912.2.2:c.1484G>A (p.RP495 *)]. This pathogenic TRIM8 variation and the combined clinical manifestations of neurogenic bladder and FSGS have not been previously reported in the literature. We report a rare Chinese case of FSGS and neurogenic bladder associated with a novel de novo heterozygous variation in the TRIM8 gene. The findings expanded the clinical spectrum of TRIM8 pathogenic variations.

Objective To evaluate the impact of thyroid-stimulating hormone (TSH) levels on tumor progression and survival in patients with uni- and multifocal T1N0M0 papillary thyroid cancer (PTC) treated with microwave ablation (MWA).Methods This retrospective study analyzed the records of 525 patients with uni- and multifocal T1N0M0 PTC who underwent MWA from January 2015 to December 2022. Patients were stratified into uni-focal (U-PTC) and multifocal (M-PTC) groups and further categorized based on post-ablation TSH levels into low (≤1 mU/L), medium (1–2 mU/L), and high (>2 mU/L) subgroups. The tumor progression rates and progression-free survival were assessed.Results In U-PTC patients, lower TSH levels were significantly associated with higher tumor progression rates (10.1%) compared to those in the medium (2.9%) and high (2.1%) TSH groups (p = .009). Conversely, in M-PTC patients, tumor progression rates did not vary significantly across TSH levels. Progression-free survival rates in U-PTC patients were notably lower at the 5-year mark in the low TSH group (85.7%) compared to the medium TSH group (96.5%, p = .046). However, progression-free survival rates in M-PTC patients showed convergence across all TSH levels by the 5-year follow-up.Conclusion Maintaining TSH levels within the normal range post-ablation may be appropriate for managing T1N0M0 PTC treated with MWA, but randomized controlled trials are needed to confirm optimal TSH targets and their impact on outcomes.

Objective To evaluate the complications associated with microwave ablation (MWA) in treating persistent/recurrent hyperparathyroidism (HPT) post-surgical or ablative treatments.Materials and methods From January 2015 to December 2022, 87 persistent/recurrent HPT patients (primary HPT [PHPT]: secondary HPT [SHPT] = 13:74) who underwent MWA after surgical or ablative treatment were studied. Grouping was based on ablation order (initial vs. re-MWA), prior treatment (parathyroidectomy [PTX] vs. MWA), and etiology (PHPT vs. SHPT). The study focused on documenting and comparing treatment complications and analyzing major complication risk factors.Result Among the 87 patients, the overall complication rate was 17.6% (15/87), with major complications at 13.8% (12/87) and minor complications at 3.4% (3/87). Major complications included recurrent laryngeal nerve (RLN) palsy (12.6%) and Horner syndrome (1.1%), while minor complications were limited to hematoma (3.4%). Severe hypocalcemia noted in 21.6% of SHPT patients. No significant differences in major complication rates were observed between initial and re-MWA groups (10.7% vs. 13.8%, p = 0.455), PTX and MWA groups (12.5% vs. 15.4%, p = 0.770), or PHPT and SHPT groups (15.4% vs. 13.5%, p > 0.999). Risk factors for RLN palsy included ablation of superior and large parathyroid glands (>1.7 cm). All patients recovered spontaneously except for one with permanent RLN palsy in the PTX group (2.1%).Conclusion Complication rates for MWA post-surgical or ablative treatments were comparable to initial MWA rates. Most complications were transient, indicating MWA as a viable and safe treatment option for persistent/recurrent HPT patients.

Objective To assess the feasibility, efficacy, and safety of microwave ablation in treating follicular thyroid neoplasms and suspicious follicular thyroid neoplasms.Methods In this retrospective study, the data of patients treated with microwave ablation for follicular neoplasms from December 2016 to January 2024 were summarized. The changes in nodule size, volume, technical success rate, disease progression, complete tumor resolution, thyroid function, and complications post-ablation were evaluated.Results Seventy-four patients (15 men, 59 women; mean age 46.3 ± 15.2 years) with follicular neoplasms were included. Over a median follow-up of 13 months, complete ablation was achieved, giving a 100% technical success rate. At the first month post-ablation, the maximum diameter of nodules showed no significant change (p = 0.287). From the third month, both maximum diameter and volume significantly decreased (p 0.05). The complication and side effect rates were 8.1% and 4.1%, respectively.Conclusions Initial findings suggest microwave ablation is an effective and safe treatment for follicular neoplasms, with low incidences of disease progression and complications, while maintaining thyroid function.

Objective Thermal ablation (TA) is a safe and effective treatment for benign thyroid nodules (BTNs). However, there has been no consensus on the optimal maximum diameter (MD) of BTNs for TA. This study aimed to identify the optimal MD of BTNs for TA based on complete disappearance rate after TA.Materials and methods This retrospective study included 639 BTNs treated with TA from June 2014 to January 2022. The complete disappearance rate of BTNs after TA was summarized, related influencing factors were explored, and the optimal MD of BTNs for TA was identified.Results At the final follow-up (median: 40 months, range: 24–95 months), the overall volume reduction rate was 95.4 ± 9.0%, and 50.5% of the BTNs (323/639) completely disappeared. The MD was significantly negatively correlated with complete disappearance (odds ratio 0.89, 95% confidence interval 0.87–0.92; p 25.0 mm had a greater complication rate (6.5% vs. 2.4%, p = 0.012).Conclusions The MD of BTNs was negatively correlated with complete disappearance after TA; an MD > 25.0 mm indicated a reduced likelihood of complete disappearance compared with an MD ≤ 25.0 mm. An MD of 25.0 mm is an appropriate threshold of BTNs for TA on the basis of complete disappearance rate.

Background Fibrotic metabolic dysfunction-associated steatohepatitis (MASH) is a condition at risk of progressing to advanced liver disease. We examined whether an innovative exhaled nitric oxide (eNO) breath test (BT) can accurately diagnose fibrotic MASH without requiring blood tests.Methods One hundred and forty-seven patients with MASH were recruited, and all tests were undertaken within 1 week of recruitment. With fibrotic MASH (NAS ≥ 4 and fibrosis stage ≥ 2) as the main outcome indicator, the diagnostic efficacy of eNO in identifying fibrotic MASH was compared to other validated models for advanced fibrosis requiring venesection, namely FAST, Agile 3+, and FIB-4 scores.Results The mean age was 40.36 ± 12.28 years, 73.5% were men. Mean body mass index was 28.83 ± 4.31 kg/m2. The proportion of fibrotic MASH was 29.25%. The area under the receiver operating curve for eNO in diagnosing fibrotic MASH was 0.737 [95% CI 0.650–0.823], which was comparable to FAST (0.751 [0.656–0.846]), Agile 3+ (0.764 [0.670–0.858]), and FIB-4 (0.721 [0.620-0.821]) (all DeLong test p > 0.05). A cut-off of eNO 13.5 ppb provided a specificity of 91.3% and a positive predictive value of 65.4% for ruling-in fibrotic MASH. Sensitivity analyses demonstrated that the diagnostic efficacy of eNO was similar across characteristics such as age. Moreover, adding vibration-controlled transient elastography-LSM (liver stiffness measurement) reduced the uncertainty interval from 46.9% to 39.5%.Conclusions The eNO-BT is a promising simple test for non-invasively identifying fibrotic MASH, and its performance is further improved by adding LSM measurement.

We designed this study to identify potential diagnostic and prognostic markers for lung adenocarcinoma (LUAD). Four gene expression profiles were downloaded from GEO and merged into a training cohort, and those genes that were differentially expressed between LUAD and normal samples were selected. We performed LASSO regression, SVM-RFE, and ROC curve analyses, and external validations were conducted using the GSE115002 dataset, TCGA + GTEx datasets, and tissue microarrays (TMAs) of 56 patients with LUAD from our hospital. Subsequent analyses included survival analyses, Cox regression, CIBERSORT, CCK-8, colony formation, and flow cytometry analyses. We observed that the expression of SH3GL2, CAV1, and GPC3 was reduced in LUAD samples in comparison to normal samples. Therefore, these genes were identified as diagnostic markers for LUAD, and validated using the GSE115002 and TCGA + GTEx datasets (AUC > 0.86 for all three). Notably, lower GPC3 expression levels were associated with worse prognoses. And GPC3 is an independent prognostic factor for LUAD; TMA analysis confirmed low GPC3 expression in tumors. Moreover, GPC3 overexpression inhibited cell viability and clonality but not cell apoptosis. In conclusion, we infer that GPC3 could serve as both a diagnostic and prognostic marker for LUAD.

Objective: To analyze the hematological phenotype and genotype of HbA2: c.96-2A > G carriers.Methods: The blood routine parameters and hemoglobin electrophoresis of rare cases were analyzed and identified by PCR combined with reverse dot blot (RBD-PCR), GAP-PCR and DNA sequencing.Results: Among the 7 patients, one adult patient had normal hemoglobin levels, with slightly decreased mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). Hb Bart's band was found in 6 neonates by hemoglobin electrophoresis, of which the content of Hb Bart's band in 1 neonate was 15.80%, and the content of Hb Bart's band in the other 5 neonates was 0.30%–0.90%. The results of genetic analysis showed that all the 7 patients had HbA2: c.96-2A > G (IVS-I-116A > G) mutation, in which 1 case was compounded with – SEA deletion.Conclusion: HbA2: c.96-2A > G mutation carriers exhibit the phenotype of α-thalassemia, and when the HbA2:c.96-2A > G mutation is combined with – SEA deletion, an intermediate phenotype of anemia is produced.

Abstract Background We aimed to gain insight into the response mechanism of alfalfa (Medicago sativa) to drought stress by recognizing and analyzing drought-responsive genes in the roots of different root types of alfalfa. The rhizomatous-rooted M. sativa cv.‘Qingshui’ (QS), tap-rooted M. sativa cv.‘Longdong’ (LD), and creeping-rooted M. varia cv. ‘Gongnong No. 4’ (GN) were used to analyze the transcriptome information and physiological characteristics of the root systems of the cultivars under simulated drought stress using PEG-6000. Results It was found that aridity caused a significant increase in the content of osmotic stress substances and antioxidant enzyme activity. The content of malondialdehyde (MDA) in QS was lower than that in LD and GN under moisture stress, indicating a stronger accumulation capacity of osmotic regulatory substances. Based on sequencing results, 14,475, 9336, and 9243 upregulated DEGs from QS, LD, and GN were annotated into 26, 29, and 28 transcription factor families, respectively. QS showed more DEGs than LD and GN. KEGG enrichment analysis identified that DEGs were significantly enriched in metabolic pathways such as amino acid biosynthesis, phenylpropanoid biosynthesis, plant hormone signaling transduction, and MAPK pathways. This suggests a strong correlation between these pathways and drought stress. The results also show that genes associated with ABA hormone signaling (MS. gene93372, MS. gene072046, and MS. gene012975) are crucial for plant’s adaptation to drought stress. Conclusions These genes, such as serine/threonine protein kinases and abscisic acid receptors, play a crucial role in plant hormone signaling and MAPK pathways. They could serve as potential candidate genes for drought resistance research in alfalfa, providing a molecular foundation for studying drought resistance. Graphical Abstract

Abstract Immune checkpoint inhibitors (ICIs) have become an important cornerstone of many tumour treatments. However, the toxicity profile of immune-chemotherapy combination treatment approaches among older adult cancer patients is still unclear. Patients with any cancer who received camrelizumab-based immunotherapy were eligible for inclusion. The primary endpoints were adverse events (AEs) and immune-related adverse events (irAEs), which were defined based on Naranjo's algorithm. Patients were stratified by age (≥ 70 years and

Objective: The objective of this study is to explore the optimal ratio of Glycyrrhiza Radix (GR, Glycyrrhizae radix et Rhizoma) and Platycodonis Radix (PR, Platycodon grandiflorum A. DC) and its potential mechanism for treating respiratory syncytial virus (RSV) pneumonia in mice. Materials and Methods: Aqueous extracts of GR-PR with different ratios (1:1, 2:1, and 1:2 w/w) were prepared and analyzed using ultra-performance liquid chromatography coupled with a linear ion trap quadrupole Orbitrap mass spectrometry (UPLC/LTQ-Orbitrap-MS). The effects of various ratios of GR-PR were investigated in BALB/c mice. Changes in body weight were recorded, histopathology was evaluated, and relative mRNA levels of inflammatory mediators were measured. In addition, lipidomic analysis was performed to investigate the effects of GR-PR on lipids and related signaling pathways. Results: The aqueous extracts of GR-PR improved body weight and reduced lung inflammation compared to the RSV group, with the optimal therapeutic effect achieved with a 1:2 ratio of GR to PR. RSV infection disrupted several serum lipids, particularly sphingomyelin (SM) and ceramide (CER), which were partially restored by GR-PR administration. Overall, GR-PR significantly improved the metabolic disorder of SM-CER-induced inflammation and apoptosis, along with decreased mRNA levels of caspase-1, nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3), and toll-like receptor 3 (TLR3), and protein expression of NLRP3, pro-caspase-1, apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), interleukin-1β (IL-1β), IL-18, gasdermin D (GSDMD), nuclear factor kappa-B (NF-κB), Bcl2-associated X protein (BAX), caspase-3, and caspase-8. The involvement of the TLR3-NF-κB-NLRP3 signaling pathway in this process was confirmed. Conclusions: The aqueous extracts of GR-PR, particularly at a ratio of 1:2, demonstrate potential therapeutic benefits for RSV-induced pneumonia by improving lipid metabolism and inhibiting the activation of TLR3-NF-κB-NLRP3 signaling pathway.

Objective: Identification of heavy menstrual bleeding (HMB) cases in primary care settings is often done by using pictorial blood assessment charts (PBAC). The study aims to highlight the challenge of assessing blood loss, to develop a standardized method to efficiently customize a patient-reported pictorial chart, to validate the tool produced with our proposed method, and to demonstrate the feasibility of using PBACs in settings where resources are scarce. Materials and methods: Using blood samples and feedback from 21 women aged 30–51 years, we followed guidelines suggested in the literature, developed a method to produce PBACs for regular, long and night sizes, and had 9 participants testuse them. Linear regression analysis was performed to determine the correlation between participants’ scores and menstrual blood weight. Results: The study demonstrated the feasibility of customizing product-sensitive and size-specific pictorial charts by adopting essential steps including collecting menstrual blood with menstrual cups, employing fluid application techniques, and using sanitary pads as icons for easy identification. Linear regression analyses of score versus blood weight showed that the recorded blood weight was around 95% of the scored values (R2 = 0.9428, 0.947, and 0.9508, respectively; p

Abstract Neoadjuvant chemotherapy (NACT) is a viable therapeutic option for women diagnosed locally advanced cervical cancer (LACC). However, the factors influencing pathological response are still controversial. We collected pair specimens of 185 LACC patients before and after receiving NACT and conducted histological evaluation. 8 fresh tissues pre-treatment were selected from the entire cohort to conducted immune gene expression profiling. A novel pathological grading system was established by comprehensively assessing the percentages of viable tumor, inflammatory stroma, fibrotic stroma, and necrosis in the tumor bed. Then, 185 patients were categorized into either the good pathological response (GPR) group or the poor pathological response (PPR) group post-NACT, with 134 patients (72.4%, 134/185) achieving GPR. Increasing tumor-infiltrating lymphocytes (TILs) and tumor-infiltrating lymphocytes volume (TILV) pre-treatment were correlated with GPR, with TILV emerging as an independent predictive factor for GPR. Additionally, CIBERSORT analysis revealed noteworthy differences in the expression of immune makers between cPR and non-cPR group. Furthermore, a significantly heightened density of CD8 + T cells and a reduced density of FOXP3 + T cells were observed in GPR than PPR. Importantly, patients exhibiting GPR or inflammatory type demonstrated improved overall survival and disease-free survival. Notably, stromal type was an independent prognostic factor in multivariate analysis. Our study indicates the elevated TILV in pre-treatment specimens may predict a favorable response to NACT, while identifying stromal type in post-treatment specimens as an independent prognostic factor. Moreover, we proposed this pathological grading system in NACT patients, which may offer a more comprehensive understanding of treatment response and prognosis.

Abstract Chemotherapy in combination with immunotherapy has gradually shown substantial promise to increase T cell infiltration and antitumor efficacy. However, paclitaxel in combination with immune checkpoint inhibitor targeting PD-1/PD-L1 was only used to treat a small proportion of metastatic triple-negative breast cancer (TNBC), and the clinical outcomes was very limited. In addition, this regimen cannot prevent paclitaxel-induced peripheral neuropathy. Therefore, there was an urgent need for a novel target to enhance the antitumor activity of paclitaxel and alleviate chemotherapy-induced peripheral neuropathy in breast cancer. Here, we found that Dickkopf-1 (DKK1) expression was upregulated in multiply subtypes of human breast cancer specimens after paclitaxel-based chemotherapy. Mechanistic studies revealed that paclitaxel promoted DKK1 expression by inducing EGFR signaling in breast cancer cells, and the upregulation of DKK1 could hinder the therapeutic efficacy of paclitaxel by suppressing the infiltration and activity of CD8+ T cells in tumor microenvironment. Moreover, paclitaxel treatment in tumor-bearing mice also increased DKK1 expression through the activation of EGFR signaling in the primary sensory dorsal root ganglion (DRG) neurons, leading to the development of peripheral neuropathy, which is charactered by myelin damage in the sciatic nerve, neuropathic pain, and loss of cutaneous innervation in hindpaw skin. The addition of an anti-DKK1 antibody not only improved therapeutic efficacy of paclitaxel in two murine subtype models of breast cancer but also alleviated paclitaxel-induced peripheral neuropathy. Taken together, our findings providing a potential chemoimmunotherapy strategy with low neurotoxicity that can benefit multiple subtypes of breast cancer patients.

PRKAG2 is required for the maintenance of cellular energy balance. PRKAG2-AS1, a long non-coding RNA (lncRNA), was found within the promoter region of PRKAG2. Despite the extensive expression of PRKAG2-AS1 in endothelial cells, the precise function and mechanism of this gene in endothelial cells have yet to be elucidated. The localization of PRKAG2-AS1 was predominantly observed in the nucleus, as revealed using nuclear and cytoplasmic fractionation and fluorescence in situ hybridization. The manipulation of PRKAG2-AS1 by knockdown and overexpression within the nucleus significantly altered PRKAG2 expression in a cis-regulatory manner. The expression of PRKAG2-AS1 and its target genes, PRKAG2b and PRKAG2d, was down-regulated in endothelial cells subjected to oxLDL and Hcy-induced injury. This finding suggests that PRKAG2-AS1 may be involved in the mechanism behind endothelial injury. The suppression of PRKAG2-AS1 specifically in the nucleus led to an upregulation of inflammatory molecules such as cytokines, adhesion molecules, and chemokines in endothelial cells. Additionally, this nuclear suppression of PRKAG2-AS1 facilitated the adherence of THP1 cells to endothelial cells. We confirmed the role of nuclear knockdown PRKAG2-AS1 in the induction of apoptosis and inhibition of cell proliferation, migration, and lumen formation through flow cytometry, TUNEL test, CCK8 assay, and cell scratching. Finally, it was determined that PRKAG2-AS1 exerts direct control over the transcription of PRKAG2 by its binding to their promoters. In conclusion, downregulation of PRKAG2-AS1 suppressed the proliferation and migration, promoted inflammation and apoptosis of endothelial cells, and thus contributed to the development of atherosclerosis resulting from endothelial cell injury.

Abstract KNOXs, a type of homeobox genes that encode atypical homeobox proteins, play an essential role in the regulation of growth and development, hormonal response, and abiotic stress in plants. However, the KNOX gene family has not been explored in sweet potato. In this study, through sequence alignment, genomic structure analysis, and phylogenetic characterization, 17, 12 and 11 KNOXs in sweet potato (I. batatas, 2n = 6x = 90) and its two diploid relatives I. trifida (2n = 2x = 30) and I. triloba (2n = 2x = 30) were identified. The protein physicochemical properties, chromosome localization, phylogenetic relationships, gene structure, protein interaction network, cis-elements of promoters, tissue-specific expression and expression patterns under hormone treatment and abiotic stresses of these 40 KNOX genes were systematically studied. IbKNOX4, -5, and − 6 were highly expressed in the leaves of the high-yield varieties Longshu9 and Xushu18. IbKNOX3 and IbKNOX8 in Class I were upregulated in initial storage roots compared to fibrous roots. IbKNOXs in Class M were specifically expressed in the stem tip and hardly expressed in other tissues. Moreover, IbKNOX2 and − 6, and their homologous genes were induced by PEG/mannitol and NaCl treatments. The results showed that KNOXs were involved in regulating growth and development, hormone crosstalk and abiotic stress responses between sweet potato and its two diploid relatives. This study provides a comparison of these KNOX genes in sweet potato and its two diploid relatives and a theoretical basis for functional studies.

Abstract Aim To explore the views and experiences of formal caregivers caring for older inpatients with physical disabilities. Methods It was a qualitative phenomenological study. Using purposive sampling, twelve formal caregivers were chosen in a tertiary comprehensive hospital in Hangzhou, China. Semi-structured, face-to-face interviews were conducted, guided by open-ended questions that focused on gaining rich insights into participants’ views and experiences. Coding reliability thematic analysis was used to guide data analysis and categorize, based on Lazarus and Folkman’s theory of transactional coping. Results Four themes emerged from the data analysis: (1) Caregiving Threats. (2) motivations. (3) Responsibility Management. (4) Fear. Conclusion Despite facing significant pressure at work, formal caregivers of elderly inpatients with physical disabilities possess the drive and various coping strategies to excel in their role. Identifying caregivers’ experiences of care can be helpful in improving resilience to stress and maintaining stability in formal caregivers.