Caudal-Type Homeobox Transcription Factor 2 is a Favorable Prognostic Indicator in Stage II and III Gastric Cancer Following Curative Surgery.

Background: The study explored the prognostic value of caudal-type homeobox transcription factor 2 (CDX2) in stage II and III gastric cancer. Methods: This study evaluated the expression level of CDX2 in gastric cancer in a hospital cohort (n=197) using immunohistochemistry. According to a semiquantitative score used to determine CDX2 expression, the cases were divided into a low CDX2 group (116 cases) and a high CDX2 group (81 cases). The RNA-seq expression data from 291 patients with stage II and III gastric cancer from The Cancer Genome Atlas (TCGA) cohort were used to verify the immunohistochemistry results. Based on the median CDX2 expression value, the TCGA patients were divided into a low CDX2 group (145 cases) and a high CDX2 group (146 cases). The relationships among CDX2 expression and clinicopathological features were determined using the Chi-square test. Cox proportional hazards regression models were applied to estimate the independent prognostic factors. The probability of survival was determined using the Kaplan-Meier method and Log rank tests. Results: Based on the Cox multivariate analysis, CDX2 was the independent prognostic factor in the hospital and TCGA cohorts. In the hospital cohort, CDX2 expression was associated with an improved DFS (hazard ratio [HR] = 0.4076, 95% CI, 0.2675-0.6210, P = 0.0001) and OS (HR = 0.4183, 95% CI, 0.2744-0.6375, P = 0.0002). In the TCGA cohort, CDX2 expression also was associated with an improved DFS (HR = 0.5948, 95% CI, 0.4153-0.8521, P = 0.0054) and OS (HR = 0.5976, 95% CI, 0.4172-0.8561, P = 0.0058). Furthermore, the CDX2 expression level was correlated with an improved DFS (P = 0.0025) and OS (P = 0.0015) using the Kaplan-Meier Plotter database for gastric cancer. Conclusion: CDX2 is a potential prognostic biomarker for stage II and III gastric cancer. In addition, CDX2 positive cancer patients are more likely to have resectable tumors and exhibit better survival rates.

Evolution of the Moral Lexicon.

Morality is central to social well-being and cognition, and moral lexicon is a key device for human communication of moral concepts and experiences. How was the moral lexicon formed? We explore this open question and hypothesize that words evolved to take on abstract moral meanings from concrete and grounded experiences. We test this hypothesis by analyzing semantic change and formation of over 800 words from the English Moral Foundations Dictionary and the Historical Thesaurus of English over the past hundreds of years. Across historical text corpora and dictionaries, we discover concrete-to-abstract shifts as words acquire moral meaning, in contrast with the broad observation that words become more concrete over time. Furthermore, we find that compound moral words tend to be derived from a concrete-to-abstract shift from their constituents, and this derivational property is more prominent in moral words compared to alternative compound words when word frequency is controlled for. We suggest that evolution of the moral lexicon depends on systematic metaphorical mappings from concrete domains to the moral domain. Our results provide large-scale evidence for the role of metaphor in shaping the historical development of the English moral lexicon.

Bivalves under extreme weather events: A comparative study of five economically important species in the South China sea during marine heatwaves.

Marine heatwaves (MHWs) are increasing in frequency and intensity, threatening marine organisms and ecosystems they support. Yet, little is known about impacts of intensifying MHWs on ecologically and economically important bivalves cultured in the South China Sea. Here, we compared survival and physiological responses of five bivalve species, Pinctada fucata, Crassostrea angulata, Perna viridis, Argopecten irradians and Paphia undulata, to two consecutive MHWs events (3 days of thermal exposure to + 4 °C or + 8 °C, following 3 days of recovery under ambient conditions). While P. fucata, P. viridis, and P. undulata are native to the South China Sea region, C. angulata and A. irradians are not. Individuals of P. fucata, C. angulata and P. viridis had higher stress tolerance to MHWs than A. irradians and P. undulata, the latter already experiencing 100% mortality under +8 °C conditions during the first event. With increasing intensity of MHWs, standard metabolic rates of all five species increased significantly, in line with significant depressions of function-related energy-metabolizing enzymes (CMA, NKA, and T-ATP). Likewise, activities of antioxidant enzymes (SOD, CAT, and MDA) and shell mineralization-related enzymes (AKP and ACP) responded significantly to MHWs, despite species-specific performances observed. These findings demonstrate that some bivalve species can likely fail to accommodate intensifying MHWs events in the South China Sea, but some may persist. If this is the case, then one would expect substantial loss of fitness in bivalve aquaculture in the South China Sea under intensifying MHWs conditions.

BRCA1 promotes repair of DNA damage in cochlear hair cells and prevents hearing loss.

Cochlear hair cells (HCs) sense sound waves and allow us to hear. Loss of HCs will cause irreversible sensorineural hearing loss. It is well known that DNA damage repair plays a critical role in protecting cells in many organs. However, how HCs respond to DNA damage and how defective DNA damage repair contributes to hearing loss remain elusive.In this study, we showed that cisplatin induced DNA damage in outer hair cells (OHCs) and promoted OHC loss, leading to hearing loss in mice of either sex. Cisplatin induced the expression of Brca1, a DNA damage repair factor, in OHCs. Deficiency of Brca1 induced OHC and hearing loss, and further promoted cisplatin-induced DNA damage in OHCs, accelerating OHC loss. This study provides the first in vivo evidence demonstrating that cisplatin mainly induces DNA damage in OHCs and that BRCA1 promotes repair of DNA damage in OHCs and prevents hearing loss. Our findings not only demonstrate that DNA-damage inducible agent generates DNA damage in postmitotic HCs, but also suggest that DNA repair factors, like BRCA1, protect postmitotic HCs from DNA-damage induced cell death and hearing loss.Significance statement Sensorineural hearing loss is the most severe hearing loss caused by irreversible loss of cochlear hair cells. Hair cells are vulnerable to aging and ototoxic drug. Though DNA damage repair plays a critical role in protecting cells in many organs, it is poorly understood how DNA damage is repaired in hair cells. This study provides the first in vivo evidence demonstrating that cisplatin mainly induces DNA damage in outer hair cells and that BRCA1 promotes repair of DNA damage in outer hair cells and prevents outer hair cell loss as well as hearing loss.

Gentiopicroside Ameliorates Sepsis-Induced Acute Lung Injury via Inhibiting Inflammatory Response.

Sepsis is a systemic inflammatory reaction syndrome caused by infections. Acute lung injury (ALI) occurs first and most frequently in patients with sepsis. Gentiopicroside (GPS), which originates mostly from Gentiana, is classified as a secoiridoid glycosides. Terpenoid glycosides have various biological effects, including liver protection, blood glucose and cholesterol level management, and anti-inflammatory and antitumor effects. However, presently, the biochemical foundation and mechanism of the anti-inflammatory effects of GPS in sepsis-induced ALI have not been explained. In the present study, we established a rat model of sepsis ALI induced by cecal ligation and puncture. This enables us to observe the effects of GPS therapy, which significantly reduced the inflammatory response (TNF-α, IL-1ß, and IL-6), nitrogen stress, oxidative stress, and severity of ALI at both the whole animal and molecular levels. In addition, GPS ameliorates LPS-induced ALI via regulation of inflammatory response and cell proptosis in BEAS-2B. This study provides a theoretical basis for treating sepsis-induced ALI with GPS.

Experimental progress in Eu(Al,Ga)4topological antiferromagnets.

The non-trivial magnetic and electronic phases occurring in topological magnets are often entangled, thus leading to a variety of exotic physical properties. Recently, the BaAl4-type compounds have been extensively investigated to elucidate the topological features appearing in their real- and momentum spaces. In particular, the topological Hall effect and the spin textures, typical of the centrosymmetric Eu(Al,Ga)4family, have stimulated extensive experimental and theoretical research. In this topical review, we discuss the latest findings regarding the Eu(Al,Ga)4topological antiferromagnets and related materials, arising from a vast array of experimental techniques. We show that Eu(Al,Ga)4represents a suitable platform to explore the interplay between lattice-, charge-, and spin degrees of freedom, and associated emergent phenomena. Finally, we address some key questions open to future investigation.

Feasibility and safety of transarterial chemoembolization in patients with liver cancer via the distal radial approach: a single-center retrospective cohort study.

Background: The femoral artery is the standard route for transarterial chemoembolization (TACE); however, it is negatively associated with the quality of life of patients, and carries an increased risk of deep vein thrombosis in the lower limbs. We employed the distal radial approach to TACE to assess its feasibility and safety. Methods: We conducted a retrospective study at the First Hospital of Jilin University from August 1, 2020 to October 31, 2023. To be eligible for inclusion in the study, the patients had to meet the following main inclusion criteria: (I) have undergone a preoperative imaging (abdominal computed tomography enhancement or magnetic resonance dynamic enhancement) examination, or have a pathologically confirmed diagnosis of primary liver cancer, and a Child-Pugh score of A or B; and (II) have undergone distal radial artery puncture. The primary endpoint of this study was the success rate of distal radial artery puncture. The secondary endpoints were complications and the duration of the puncture. Results: Among the 343 patients with primary liver cancer (of whom 236 were male and 107 were female), a total of 1,315 distal radial artery punctures were attempted. The success rate was remarkably high at 95.13% (1,251/1,315), with only 64 cases requiring an alternative approach due to failed puncture. The average puncture duration was 20±7.43 minutes. No bleeding and hematoma, no arterial dissection and pseudoaneurysm formation were observed on ultrasound, and the radial pulse was palpable in all patients, highlighting the safety of the procedure. Further, no adverse events of vascular occlusion were observed among the 12 patients who received 6 or more punctures, indicating the sustainability of the distal radial artery access under the premise of adequate vascular protection. The development of this technique requires a learning curve of at least 50 cases to break through the learning baseline and be proficient in distal radial artery blind puncture. This may be the reason why many interventional physicians are reluctant to perform this procedure, adapting to the femoral approach with a shorter learning curve. Conclusions: The distal radial artery approach is feasible and safe in hepatic arterial chemoembolization, and should be widely promoted in TACE.

Enhancing chiral molecule detection: A weak measurement approach utilizing two-dimensional information.

This study addresses the critical need for high purity chiral molecules in biological systems by overcoming the challenges associated with the quantitative detection of chiral molecules and their enantiomeric mixtures. We developed an innovative detection approach that leverages the two-dimensional information gleaned from natural optical rotation (NOR) and Faraday optical rotation (FOR) under magnetic fields in chiral molecules, combined with an ultrahigh-resolution weak measurement sensor. This novel weak measurement system achieves unparalleled accuracy in detecting spin angles, with a precision of 1.86 × 10-5°. Notably, our method introduces no chemical reactions or interference with the substances under test. It offers enhanced discrimination capabilities through the dual-dimensional analysis of both natural and Faraday optical rotation, alongside a simple and compact sensor design. Conclusively, our study introduces a novel, high-precision, and multi-dimensional optical detection paradigm for chiral molecules. By incorporating Faraday rotation in the presence of a magnetic field, we expand the informational dimensionality accessible to the original weak measurement sensor, facilitating the quantitative analysis of chiral molecules and their enantiomers. This breakthrough not only furnishes a novel instrument for the exploration and development of chiral pharmaceuticals but also propels the advancement of weak measurement sensing technology forward.

A biomimetic skin microtissue biosensor for the detection of fish parvalbumin.

In this paper, a biomimetic skin microtissue biosensor was developed based on three-dimensional (3D) bioprinting to precisely and accurately determine fish parvalbumin (FV). Based on the principle that allergens stimulate cells to produce ONOO- (peroxynitrite anion), a screen-printed electrode for the detection nanomolar level ONOO- was innovatively prepared to indirectly detect FV based on the level of ONOO- release. Gelatin methacryloyl (GelMA), RBL-2H3 cells, and MS1 cells were used as bio-ink for 3D bioprinting. The high-throughput and standardized preparation of skin microtissue was achieved using stereolithography 3D bioprinting technology. The printed skin microtissues were put into the self-designed 3D platform that integrated cell culture and electrochemical detection. The experimental results showed that the sensor could effectively detect FV when the optimized ratio of RBL-2H3 to MS1 cells and allergen stimulation time were 2:8 and 2 h, respectively. The linear detection range was 0.125-3.0 µg/mL, and the calculated lowest detection limit was 0.122 µg/mL. In addition, the sensor had excellent selectivity, specificity, stability, and reliability. Thus, this study successfully constructed a biomimetic skin microtissue electrochemical sensor for PV detection.

Integrative gene regulatory network analysis discloses key driver genes of fibromuscular dysplasia.

Fibromuscular dysplasia (FMD) is a poorly understood disease affecting 3-5% of adult females. The pathobiology of FMD involves arterial lesions of stenosis, dissection, tortuosity, dilation and aneurysm, which can lead to hypertension, stroke, myocardial infarction and even death. Currently, there are no animal models for FMD and few insights as to its pathobiology. In this study, by integrating DNA genotype and RNA sequence data from primary fibroblasts of 83 patients with FMD and 71 matched healthy controls, we inferred 18 gene regulatory co-expression networks, four of which were found to act together as an FMD-associated supernetwork in the arterial wall. After in vivo perturbation of this co-expression supernetwork by selective knockout of a top network key driver, mice developed arterial dilation, a hallmark of FMD. Molecular studies indicated that this supernetwork governs multiple aspects of vascular cell physiology and functionality, including collagen/matrix production. These studies illuminate the complex causal mechanisms of FMD and suggest a potential therapeutic avenue for this challenging disease.

Diffuse skin erythematous plaque as a manifestation of epithelioid hemangioendothelioma: A case report.

Epithelioid hemangioma (EHE) is a rarely malignant tumor originating from the vascular endothelium. Morphological manifestations and immunohistochemical staining results are key to diagnosing EHE. Herein, we present a case of cutaneous involment in a recurrence of EHE. A 75-year-old woman presented with a month-long history of persistent erythematous plaque and pain in the left shoulder. Skin biopsy specimen revealed epithelioid tumor cells containing abundant eosinophilic cytoplasm. Immunohistochemical staining confirmed a recurrence of EHE involving the skin. Subsequently, recombinant human endostatin was administered. At the 10-day follow-up, the cutaneous plaque had improved, and the pain had resolved. When presenting as a local painful erythematous plaque, the possibility of skin involvement in a malignant tumor should be considered. Early diagnosis and early systemic therapy have an important impact on the overall survival of patients with EHE.

Quality control of traditional Chinese medicine Chelidonii herba based on 2D-Q-NMR.

Chelidonii herba is a traditional Chinese medicinal herb with effects including antispasmodic, analgesic, antitussive, and bronchodilator properties. Alkaloids are the main bioactive ingredients in Chelidonii herba. In this study, a two-dimensional nuclear magnetic resonance (Heteronuclear Singular Quantum Correlation, HSQC-2D-NMR) technique was employed to quantitatively analyze the total alkaloid content and three major active alkaloid monomers in Chelidonii herba from eleven different sources. The quantification results of the three monomeric alkaloids were also verified using conventional quantitative control methods such as HPLC. Experimental findings indicate that the total alkaloid content is not directly correlated with the content of the three monomeric alkaloids. Furthermore, the content of any individual monomeric alkaloid does not accurately reflect the overall quality of Chelidonii herba. It was demonstrated that the 2D-Q-NMR NMR can be applied as an alternative method. While maintaining the same levels of accuracy and precision, the 2D-Q-NMR method is simpler to operate and provides more comprehensive results with higher reproducibility in some cases.

In vitro digestion and antioxidant activity of Xuan-Mugua (Chaenomeles fruit) peel and pulp phenolics.

Since time immortal, people have used the well-known Chinese Chaenomeles fruit Xuan-Mugua for both traditional medicine and nourishment. With an aim to explore the digestive and antioxidant properties of the phenolics, Xuan-Mugua peel and pulp were extracted, digested and analyzed in vitro. Our results indicated that the total phenolics content (TPC), total flavonoids content (TFC) and the antioxidant activity of the peel were 3.24-8.89 times higher than that of pulp. The contents and activity of the peel and pulp consistently dropped in the sequence of oral, gastric, and small intestine digestions, from 22.78 % to 52.16 %. With a level of 1.590 ± 0.060 and 0.395 ± 0.015 mg g-1 dried weight in the peel and pulp, respectively, chlorogenic acid was the primary phenolic ingredient in Xuan-Mugua, with a promising recovery (81.39-82.23 %) during the digestion. According to these results, Xuan-Mugua exhibited an appreciable level of phenolic content and antioxidant activity during digestion, making it a suitable ingredient for use in functional foods.

Factors influencing efficacy and relapse of adrenocorticotropic hormone in infantile epileptic spasms syndrome.

BACKGROUND: Infantile epileptic spasms syndrome (IESS) is a severe epileptic condition characterized by persistent uncontrolled seizures, with some children experiencing recurrent seizures despite multiple pharmacological therapies. The prognostic risk factorsassociated with IESS remain unclear. This study aimed to evaluate the factors influencing the efficacy and relapse of adrenocorticotropic hormone (ACTH) treatment for IESS in infants, as well as to assess the correlation between the Burden of Amplitudes and Epileptiform Discharges (BASED) score and clinical outcomes. METHODS: A retrospective analysis was conducted on a cohort of 88 pediatric patients diagnosed with IESS who received ACTH therapy at our hospital from February 2016 to August 2023. Patients were categorized into response (n = 47) and non-response (n = 41) groups based on their treatment response at day 28. Responders were further classified into relapse and non-relapse groups. A modified Poisson regression model and receiver operating characteristic (ROC) curves were employed to evaluate the positive predictive values. RESULTS: In this study, a total of 47 patients (53.4 %) responded to ACTH treatment. Patients in the response group demonstrated significantly greater reductions in BASED scores by day 14 of ACTH treatment, yielding an area under the curve (AUC) of 0.859 (95 % CI: 0.782-0.937, P＜0.05), with a sensitivity of 68.1 % and a specificity of 95.1 %. The optimal cut-off point was established at ≥ 2, corresponding to a Youden index of 0.632. Notably, patientswho were on anti-seizure medications (ASMs) before ACTH treatment and those with developmental delay prior to the onset of spasms exhibited lower short-term response rates (P＜0.05), although these factors did not demonstrate predictive value. Among the responders, 20 cases (42.6 %) experienced a relapse, with only those patients showing specific abnormalities on cranial magnetic resonance imaging (MRI) exhibiting a statistically higher proportion of relapse. CONCLUSION: Patients receiving ASMs before ACTH treatment and those with developmental delays prior to the onset of spasms may have a less favorable therapeutic response. A reduction in BASED scores of 2 or greater by day 14 of ACTH treatment may signify a potentially positive treatment response. Additionally, patients with IESS who present with specific abnormalities on cranial MRI may have an increased likelihood of relapse following ACTH treatment.

Non-alkaloid components with inhibitory activity against LPS induced NO production in RAW 264.7 cells isolated from the roots of Sophora flavescens.

Sophora flavescens Aiton is a plant in the Leguminosae family. As a traditional Chinese medicine, it is used to treat eczema, bloody stool, skin pruritus, and so on. By studying non-alkaloid components in the roots of S. flavescens, we obtained a total of 49 compounds (1-49), including three undescribed flavonoids (13, 15 and 18), five undescribed isopentenyl flavonoids (32, 34, 38, 39 and 48), two known coumarins (1-2), three phenolic acids (3-5), one known isopentenyl flavonoids (19-31, 33, 35-37, 40-47 and 49). On the basis of chemical evidences and spectral data analysis (UV, ECD, Optical rotation data, 1D/2D-NMR and HR-ESI-MS), the structures of undescribed compounds were elucidated. The inhibitory effect of compounds 1-49 on LPS induced NO production in RAW 264.7 cells was detected. Compounds 11, 19, 21-24, and 28-30 showed significant inhibitory effects, and the IC50 values of compounds 11 and 22 even reached 4.58 ± 0.66 and 4.53 ± 0.66 µM. This study suggests that flavonoids may be the main component that exerts anti-inflammatory effects in the non-alkaloid extraction layer of the extract from the roots of S. flavescens.

Elucidating maternal provisioning for bivalve larvae under ocean acidity extreme events.

Ocean acidity extreme (OAX) events, triggered by climate change and anthropogenic activities, are projected to become more intense and frequent in coastal ecosystems, devastating marine bivalves and ecosystems they support. Maternal effects adaptively modulate offspring performance in response to climatic stressors, but whether and to what extent they can confer offspring resistance to OAX remain largely unknown. Here, we investigated impacts of OAX on the parental and larval lipidomes of Manila clams (Ruditapes philippinarum) to add further insights into the energetic nature of maternal effects. A total of 177 significantly down-regulated lipid components (categorized into glycerolipids mainly) were shown in OAX-stressed adults compared with those reared under ambient conditions, and following parental conditioning, larvae also exhibited a further decreasing down-regulation of the glycerolipid components. Triacylglycerols were identified as the predominant composition of glycerolipids and the primary sources of energy for gonadal maturation and larvae development. Yet, larvae spawn from adults exposed to OAX had significantly lower contents of triacylglycerols than those without a prior history of parental conditioning, with the carbon chain length and unsaturation degree of the triacylglycerol components being significantly affected. The latter was also in line with significant increases in the production of triacylglycerol byproducts (diacylglycerols). Overall, our findings suggest that when OAX prevailed during reproductive seasons of Manila clams, maternal effects could be maladaptive by depressing the energetic deposition of larvae, and may not be a potential adaptive modulator of marine bivalves to cope with unprecedented environmental change.

Trajectories of cognitive function development and predictive factors in disabled middle-aged and older adults.

Objective: To explore the trajectories of cognitive function development and predictive factors in disabled middle-aged and older adults. Methods: Utilizing data from 983 disabled middle-aged and older adults in the China Health and Retirement Longitudinal Study (CHARLS) from 2013 to 2020, latent growth mixture models were constructed to analyze the categories of cognitive function development trajectories and their predictive factors. Results: The cognitive function trajectories of the disabled middle-aged and older adults were classified into three categories: rapid decline (32.6%), Slow decline (36.1%), and Stable (31.2%). Multinomial logistic regression analysis identified age, gender, residence, education, marital status, household income, sleep duration, depression, hearing ability, and social participation as predictors of these trajectories. Conclusion: There is heterogeneity in the cognitive function development trajectories among disabled middle-aged and older adults. Healthcare professionals can implement targeted health management based on the characteristics of different groups to prevent the deterioration of cognitive function in this population.

Ultrasonographic assessment of the risk of free-floating thrombus detachment in the lower extremity deep veins in patients with fracture.

OBJECTIVE: To explore the ultrasonographic features and influencing factors of free-floating thrombus (FFT) detachment in the lower extremity deep veins (LEDVs) of patients with fractures. METHODS: Clinical data of patients diagnosed with FFT in the LEDVs and implanted with an inferior vena cava filter (IVCF) in our hospital between July 2021 and August 2023 were retrospectively analysed. The patients were divided into the thrombus detachment group (the experimental group, n = 92) and the non-thrombus detachment group (the control group, n = 103) based on the presence of detached thrombus in the IVCF. The effects of thrombus echogenicity, floating degree, thrombus location, thrombin time, D-dimer and fibrinogen on thrombus shedding were analysed. The nomogram method was used to establish the model and predict the probability of delayed postoperative recovery. RESULTS: The proportions of patients with extremely hypoechoic thrombus and medium and high floating degrees increased in the experimental group compared with those in the control group, and the differences between the two groups were statistically significant (P < 0.05). Extremely hypoechoic thrombus (P = 0.021, 95 % CI: 1.109-13.748) and high (P = 0.001, 95 % CI: 3.854-28.573) and medium floating degrees (P = 0.004, 95 % CI: 1.792-13.453) were risk factors for deep veins FFT (DV FFT) detachment. The results of receiver operating characteristic curve analysis showed that the area under the curve of the model was 0.893, with a 95 % CI of 0.856-0.937, indicating a high prediction accuracy. CONCLUSION: Ultrasonographic parameters, including thrombus echogenicity and floating degree, are valuable in predicting DV FFT detachment in patients with traumatic fractures, providing references for IVCF implantation.