The expansion of MDSCs induced by exosomal PD-L1 promotes the progression of gastric cancer.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are the major factor in gastric cancer (GC) immune evasion. Nevertheless, the molecular process underlying the expansion of MDSCs induced by tumor-derived exosomes (TDEs) remains elusive. METHODS: The levels of exosomal and soluble PD-L1 in ninety GC patients were examined via enzyme-linked immunosorbent assay (ELISA) to determine their prognostic value. To investigate the correlation between exosomal PD-L1 and MDSCs, the percentage of MDSCs in the peripheral blood of 57 GC patients was assessed via flow cytometry. Through ultracentrifugation, the exosomes were separated from the GC cell supernatant and detected via Western blotting, nanoparticle tracking analysis (NTA), and transmission electron microscopy (TEM). The function of exosomal PD-L1 in MDSCs was evaluated via immunofluorescence, Western blotting and flow cytometry in a GC cell-derived xenograft (CDX) model. RESULTS: The overall survival (OS) of GC patients in the high exosomal PD-L1 group was significantly lower than that of patients in the low exosomal PD-L1 group (P = 0.0042); however, there was no significant correlation between soluble PD-L1 and OS in GC patients (P = 0.0501). Furthermore, we found that the expression of exosomal PD-L1 was positively correlated with the proportions of polymorphonuclear MDSCs (PMN-MDSCs, r = 0.4944, P < 0.001) and monocytic MDSCs (M-MDSCs, r = 0.3663, P = 0.005) in GC patients, indicating that exosomal PD-L1 might induce immune suppression by promoting the aggregation of MDSCs. In addition, we found that exosomal PD-L1 might stimulate MDSC proliferation by triggering the IL-6/STAT3 signaling pathway in vitro. The CDX model confirmed that exosomal PD-L1 could stimulate tumor development and MDSC amplification. CONCLUSIONS: Exosomal PD-L1 has the potential to become a prognostic and diagnostic biomarker for GC patients. Mechanistically, MDSCs can be activated by exosomal PD-L1 through IL-6/STAT3 signaling and provide a new strategy against GC through the use of exosomal PD-L1 as a treatment target.

Unveiling the Interplay Between Depressive Symptoms' Alleviation and Quality of Life Improvement in Major Depressive Disorder: A Network Analysis Based on Longitudinal Data.

Background: Understanding the dynamic relationship between depressive symptoms and quality of life (QOL) is essential in improving long-term outcomes for patients with Major Depressive Disorder (MDD). While previous studies often relied on cross-sectional data, there is a pressing need for stronger evidence based on longitudinal data to better inform the development of effective clinical interventions. By focusing on key depressive symptoms, such interventions have the potential to ultimately enhance QOL in individuals with MDD. Methods: This multi-center prospective study, conducted between 2016 and 2020, enrolled outpatients and inpatients diagnosed with MDD across twelve psychiatric hospitals in China. Longitudinal data on Patient Health Questionnaire - 9 (PHQ-9) and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) was analyzed using an Extended Bayesian Information Criterion (EBIC) graphical least absolute shrinkage and selection operator (gLASSO) network model to explore the connections between depressive symptom changes and QOL changes. Flow network was applied to investigate relationships between individual symptom changes and overall QOL score change, as well as daily functional independence. Results: This study included 818 participants with complete data after 8-week antidepressant treatment. Apart from the overlapping items from PHQ-9 and Q-LES-Q-SF, the three edges between "mood" (delta-QLES2) and "anhedonia" (delta-DEP1), between "physical health" (delta-QLES1) and "sleep problems" (delta-DEP3), and between "physical health" (delta-QLES1) and "sad mood" (delta-DEP2) were the most strong bridges between the cluster of depressive symptoms alleviation and the cluster of QOL change. "Anhedonia" (delta-DEP1), "sad mood" (delta-DEP2) and "loss of energy" (delta-DEP4) had the highest bridge strength between the alleviations of depressive symptoms and the total score change of Q-LES-Q-SF. Anhedonia had the greatest connection with participants' satisfaction with function in daily life. Conclusion: This study highlighted the potential for developing highly effective interventions by targeting on central symptoms, thereby to ultimately improve QOL for patients with MDD.

Real world data analysis of next-generation sequencing and corresponding clinical characteristics in thyroid tumor.

Next-generation sequencing (NGS) is of great benefit to clinical practice in terms of identifying genetic alterations. This study aims to clarify the gene background and its influence on thyroid tumor in Chinese population. NGS data and corresponding clinicopathological features (sex, age, tumor size, extrathyroidal invasion, metastasis, multifocality and TNM stage) were collected and analyzed retrospectively from 2844 individual thyroid tumor samples during July 2021 to August 2022. 2337 (82%) of the cohort possess genetic alterations including BRAF (71%), RAS (4%), RET/PTC (4%), TERT (3%), RET (2.2%) and TP53 (1.4%). Diagnostic sensitivity before surgery can be significantly increased from 0.76 to 0.91 when cytology is supplemented by NGS. Our results show that BRAF positive papillary thyroid cancer (PTC) patients tend to have elder age, smaller tumor size, less vascular invasion, more frequent tumor multifocality and significantly higher cervical lymph node metastatic rate. Mutation at RET gene codon 918 and 634 is strongly correlated with medullary thyroid cancer (MTC), However it did not display more invasive clinical characteristics. TERT positive patients are more likely to have elder age, larger tumor size, more tumor invasiveness, and more advanced TNM stage, indicating poor prognosis. Patients with TERT, RET/PTC1 and CHEK2 mutation are more susceptible to lateral lymph node metastasis. In conclusion. NGS can be a useful tool which provides practical gene evidence in the process of diagnosis and treatment in thyroid tumors.

Application of the modified Byars staged procedure for severe hypospadias repair.

This study aimed to introduce a modified Byars staged procedure and investigate its application value in patients with severe hypospadias. We retrospectively analyzed the clinical data of patients with severe hypospadias admitted to the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) between October 2012 and October 2022. In total, 31 patients underwent the conventional Byars procedure (conventional group), and 45 patients underwent the modified Byars staged procedure (modified group). Our modified strategy was built upon the standard Byars procedure by incorporating glansplasty during the first stage and employing a Y-shaped flap in conjunction with a glandular tunnel for urethroplasty during the second stage. Notably, there were no statistically significant differences in the preoperative baseline characteristics, duration of surgery, amount of blood loss, or occurrence of postoperative complications, including urethral fistula, stricture and diverticulum, or penile curvature, between the conventional and modified groups. However, there was a significantly lower incidence of coronal sulcus fistula (0 vs 16.1%, P = 0.02) and glans dehiscence (0 vs 12.9%, P = 0.02) in the surgical group than that in the conventional group. In addition, the modified group exhibited a notably greater rate of normotopic urethral opening (100.0% vs 83.9%, P = 0.01) and a higher mean score on the Hypospadias Objective Penile Evaluation (HOPE; mean ± standard error of mean: 8.6 ± 0.2 vs 7.9 ± 0.3, P = 0.02) than did the conventional group. In conclusion, the modified Byars staged procedure significantly reduced the risks of glans dehiscence and coronal sulcus fistula. Consequently, it offers a promising approach for achieving favorable penile esthetics, thereby providing a reliable therapeutic option for severe hypospadias.

Liquid nitrogen ball-milled mechanochemical modification of starches with typically selected A, B and C crystal types on multiscale structure and physicochemical properties.

This study investigated the effect of liquid nitrogen ball-milled mechanochemical treatment on multiscale structure and physicochemical properties of starches with typically selected A (rice starch, ReS), B (potato starch, PtS) and C (pea starch, PeS) crystal types. The morphology of starch samples changed from integral granules to irregular fragments, and the interaction between the exposure OH bonds led to a serious agglomeration. As the treatment times extended, the crystalline structure of starch samples was gradually destroyed, and the excessive treatment approached amorphization. Moreover, the thermal stability of starch samples showed the downward tendency; and with amorphization increased, the swelling power (SP), solubility (S), water absorption capacity (WAC), oil absorption capacity (OAC) and hydrolysis rate of starch samples gradually increased. The obtained results provided a theoretical foundation for broadening the application range of ball-milled starches with different crystal types.

Efficient Deep-Blue Organic Light-Emitting Diodes Employing Doublet Sensitization.

Fast and efficient exciton utilization is a crucial solution and highly desirable for achieving high-performance blue organic light-emitting diodes (OLEDs). However, the rate and efficiency of exciton utilization in traditional OLEDs, which employ fully closed-shell materials as emitters, are inevitably limited by spin statistical limitations and transition prohibition. Herein, a new sensitization strategy, namely doublet-sensitized fluorescence (DSF), is proposed to realize high-performance deep-blue electroluminescence. In the DSF-OLED, a doublet-emitting cerium(III) complex, Ce-2, is utilized as sensitizer for multi-resonance thermally activated delayed fluorescence emitter ν-DABNA. Experimental results reveal that holes and electrons predominantly recombine on Ce-2 to form doublet excitons, which subsequently transfer energy to the singlet state of ν-DABNA via exceptionally fast (over 108 s-1) and efficient (≈100%) Förster resonance energy transfer for deep-blue emission. Due to the circumvention of spin-flip in the DSF mechanism, near-unit exciton utilization efficiency and remarkably short exciton residence time of 1.36 µs are achieved in the proof-of-concept deep-blue DSF-OLED, which achieves a Commission Internationale de l'Eclairage coordinate of (0.13, 0.14), a high external quantum efficiency of 30.0%, and small efficiency roll-off of 14.7% at a luminance of 1000 cd m-2. The DSF device exhibits significantly improved operational stability compared with unsensitized reference device.

The influence of occupant control behaviour on thermal comfort under different heating charging modes in residential buildings in cold regions.

In China's central heating, there are two modes for calculating heating costs, which are divided into Charging by flow mode which charges according to the amount of use and Charging by area mode which charges according to the floor area. The Charging by flow mode has been increasingly adopted by numerous urban central heating buildings. Thus it is worth investigating whether occupants experience varying levels of thermal comfort under these two modes. To address this, a field test and subjective questionnaire survey were conducted on residential buildings in cold regions of China during the heating season. The study assessed 134 residential occupants utilizing radiator heating, comprising 66 in Charging by area and 68 in Charging by flow modes. A collection of 1206 valid data points was obtained, with 609 in Charging by area mode and 597 in Charging by flow mode. The findings reveal noteworthy disparities in the duration, area, and strength of heating equipment usage between the two modes. While there are no marked variances in the interior and exterior environmental conditions under both modes, residents in the Charging by flow mode experience enhanced thermal comfort, acceptability and expectation, as well as better air quality satisfaction. Perceived control can greatly enhance individuals' thermal sensation in temperatures below 18 °C and above 24 °C. The impact of perceived control on thermal expectation is linear with temperature adjustments. The heightened degree of sensing control in Charging by flow mode lowers residents' expectations of high temperatures, broadens the range of acceptable low temperatures and accomplishes energy conservation and carbon reduction while ensuring optimal comfort.

Comparative single-cell transcriptomic analysis across tissues of aging primates reveals specific autologous activation of ZNF281 to mitigate oxidative stress in cornea.

Reactive oxygen species (ROS) and oxidative stress accelerate cellular aging, but their impact on different tissues varies. The cornea, known for its robust antioxidant defense systems, is relatively resistant to age-related diseases like cancer. However, the precise mechanisms by which the cornea maintains ROS homeostasis during aging remain unclear. Through comparative single-cell transcriptomic analysis of the cornea and other tissues in young and old nonhuman primates, we identified that a ZNF281 coding transcriptomic program is specifically activated in cornea during aging. Further investigation revealed that ZNF281 forms a positive feedback loop with FOXO3 to sense elevated levels of ROS and mitigate their effects potentially by regulating the mitochondrial respiratory chain and superoxide dismutase (SOD) expression. Importantly, we observed that overexpression of ZNF281 in MSCs prevented cellular senescence. In summary, these findings open up possibilities for understanding tissue-specific aging and developing new therapies targeting ROS damage.

miR-137: a potential therapeutic target for lung cancer.

Lung cancer is a prevalent malignancy and the leading cause of cancer-related deaths, posing a significant threat to human health. Despite advancements in treatment, the prognosis for lung cancer patients remains poor due to late diagnosis, cancer recurrence, and drug resistance. Epigenetic research, particularly in microRNAs, has introduced a new avenue for cancer prevention and treatment. MicroRNAs, including miR-137, play a vital role in tumor development by regulating various cellular processes. MiR-137 has garnered attention for its tumor-suppressive properties, with studies showing its potential in inhibiting cancer progression. In lung cancer, miR-137 is of particular interest, with numerous reports exploring its role and mechanisms. A comprehensive review is necessary to consolidate current evidence. This review highlights recent studies on miR-137 in lung cancer, covering cell proliferation, migration, apoptosis, drug resistance, and therapy, emphasizing its potential as a biomarker and therapeutic target for lung cancer treatment and prognosis.

Response of soil enzymatic activity to pore structure under inversion tillage with organic materials incorporation in a Haplic Chernozem.

Soil pore structure affects microbial survival environmental conditions and thus enzyme activity. The mechanisms underlying returning organic materials on soil pore structure and enzymatic activity, however, remain unclear. We therefore conducted a field experiment in the fall of 2018 in northeastern China with a chernozem soil and four treatments: CT, conventional tillage; SCT, returning maize straw incorporation with conventional tillage; SIT, returning maize straw incorporation with inversion tillage; SMIT, returning maize straw and organic manure with inversion tillage. Soil samples were collected from the 0-15 cm and 15-35 cm layers in the fall of 2021. We used X-ray computed tomography to analyze the characteristics of pore structure and extracellular enzymatic stoichiometry to evaluate the limiting factors for soil microorganisms. Inversion tillage and organic materials incorporation can alter the micromorphological structure of entire soil layer, leading to the rearrangement of soil particles and nutrients, thereby augmenting the physicochemical properties in subsoil layer. SMIT exhibited a substantial increase in the number of macropores, porosity and fractal dimension, compared to SCT and SIT. This led to a significantly increased in soil enzyme activities of carbon and nitrogen-limited in SMIT, with increases ranging from 11.67% to 40.16% and from 8.81% to 21.43%, respectively (P < 0.05). Analysis using structural equation modeling revealed that returning organic material was conducive to the development of soil pore structure, characterized by an increase in macropores and fractal dimension and a decrease in the Euler number, had a positive correlation with soil enzyme activity. This, in turn, led to an alleviation in microbial nitrogen limitation. These results indicate that SMIT could serve as a viable choice in enhancing soil structure and fostering a favorable environment for microbial survival. Moreover, they offer essential insights into the microbial strategies responsible for the breakdown of organic matters in Hapli-Udic Cambisol.

[Construction effect of fertile cultivated layer in albic soil â Effects of inversion tillage with organic mate-rials on the redistribution of organic matter in surface layer of albic soil]. / 白浆土肥沃耕层构建效应â .不同有机物料深混对白浆土有机质在表层土壤中再分布的影响.

Soil organic matter serves as a crucial indicator for soil quality. Albic soil, characterized by a barrier layer, exhibits limitations in organic matter content, which can adversely affect crop growth and development. To elucidate the impact of deep mixing of various organic materials on the redistribution of organic matter in the surface soil of albic soil could provide theoretical and technical insights for establishing suitable plough layers for albic soil in Northeast China. We conducted a two-year positioning experiment in Shuangyashan, Heilongjiang Province with five treatments, conventional shallow tillage (0-15 cm, CK), inversion tillage (0-35 cm) without or with straw return (T35 and T35+S), inversion tillage with cattle manure (T35+M) and cattle manure plus maize straw (T35+S+M). The results showed that soil fertilization via deep mixing of organic materials to a depth of 35 cm significantly increased maize yield in albic soil, with the T35+S+M treatment demonstrating the most pronounced effect, yielding an average production of 2934.76 kg·hm-2. Compared to CK, the T35 treatment resulted in a significant 8.4% decrease in organic matter content in the tillage layer, a significant 7.6% increase in organic matter in the sub-tillage layer, and a relative richness degree of soil organic matter in the sub-tillage layer increased by 17.5%. Deep mixed return of organic materials following deep ploughing markedly increased organic matter content of the plough layer, with organic matter conversion ranging from 16.3% to 31.0%. In comparison to the T35 treatment, there was no significant increase in soil organic matter content in the T35+S tillage layer and sub-tillage layer. Conversely, soil organic matter content increased by 4.6% and 6.9% in the T35+M and T35+S+M treatments, with corresponding increase of 11.2% and 15.4% in sub-tillage layer, respectively. Additionally, the soil organic matter richness index in sub-tillage layer increased by 2.5% and 5.1%, respectively. There was a significant positive correlation between organic matter content in the entire plough layer and maize yield, with a contribution rate of 17.5%. Therefore, the utilization of organic fertilizer or a combination of organic fertilizer and straw deep mixing can quickly fertilize albic soil by increasing soil organic matter content in both the whole tillage layer (0-35 cm) and the sub-tillage layer (15-35 cm).

First-in-human robotic-assisted transcatheter mitral edge-to-edge repair for treatment of severe mitral regurgitation.

We present the first robot-assisted transcatheter mitral edge-to-edge repair (M-TEER) for the treatment of severe mitral regurgitation. 68-year-old patient presented with worsening dyspnea on exertion and intermittent palpitations (NYHA class III). Transthoracic echocardiography revealed severe functional mitral regurgitation (MR) with moderate left ventricular and left atrial enlargement. Due to the patient's high surgical risk (STS score of 8.84%), a transcatheter mitral edge-to-edge repair was planned following heart team discussion. Results: The final transesophageal echocardiography confirmed that the MR had reduced from the original severe to mild. This case report demonstrates, the feasibility of a mitral TEER system with a robotic-assisted approach, potentially paving the way for future applications in structural heart and endovascular intervention.

Multi-scale anatomical regularization for domain-adaptive segmentation of pelvic CBCT images.

BACKGROUND: Cone beam computed tomography (CBCT) image segmentation is crucial in prostate cancer radiotherapy, enabling precise delineation of the prostate gland for accurate treatment planning and delivery. However, the poor quality of CBCT images poses challenges in clinical practice, making annotation difficult due to factors such as image noise, low contrast, and organ deformation. PURPOSE: The objective of this study is to create a segmentation model for the label-free target domain (CBCT), leveraging valuable insights derived from the label-rich source domain (CT). This goal is achieved by addressing the domain gap across diverse domains through the implementation of a cross-modality medical image segmentation framework. METHODS: Our approach introduces a multi-scale domain adaptive segmentation method, performing domain adaptation simultaneously at both the image and feature levels. The primary innovation lies in a novel multi-scale anatomical regularization approach, which (i) aligns the target domain feature space with the source domain feature space at multiple spatial scales simultaneously, and (ii) exchanges information across different scales to fuse knowledge from multi-scale perspectives. RESULTS: Quantitative and qualitative experiments were conducted on pelvic CBCT segmentation tasks. The training dataset comprises 40 unpaired CBCT-CT images with only CT images annotated. The validation and testing datasets consist of 5 and 10 CT images, respectively, all with annotations. The experimental results demonstrate the superior performance of our method compared to other state-of-the-art cross-modality medical image segmentation methods. The Dice similarity coefficients (DSC) for CBCT image segmentation results is 74.6 ± 9.3 $74.6 \pm 9.3$ %, and the average symmetric surface distance (ASSD) is 3.9 ± 1.8 mm $3.9\pm 1.8\;\mathrm{mm}$ . Statistical analysis confirms the statistical significance of the improvements achieved by our method. CONCLUSIONS: Our method exhibits superiority in pelvic CBCT image segmentation compared to its counterparts.

Single-Slice Hounsfield Unit (HU) Value of the Chinese Proximal Humerus on Routine Chest CT: A Study on Opportunistically Screening for Low Bone Density / Valor de Unidad Hounsfield (HU) de Corte Único del Húmero Proximal Chino en una Tomografía Computarizada de Tórax de Rutina: Un Estudio sobre la Detección Oportunista de Baja Densidad Ósea

SUMMARY: A Study on Relationship between Single-Slice Hounsfield Unit(HU) value of the Chinese proximal humerus and Bone Mineral Density(BMD) Using Routine Chest CT and Dual-energy X-ray Absorptiometry(DEXA) was performed. Data were collected from 240 individuals who underwent DEXA and routine chest CT scans (including full images of the proximal humerus) on the same day at 967 Hospitals between January 2019 and December 2021. The method of measuring single-slice HU values of the proximal humerus on routine chest CT scans exhibited high reliability and repeatability (intraclass correlation coefficient > 0.961, P < 0.001). A strong positive correlation was observed between single-slice HU values of the proximal humerus and DEXA results, with the 20-mm HU value demonstrating the highest correlation. Across different BMI groups, the Area Under Curve (AUC) for the 20-mm HU value was consistently the largest (AUC=0.701- 0.813, P< 0.05). Therefore, the 20-mm HU value can be considered a reliable reference for the opportunistic screening of low BMD, with reference values of -4HU for underweight individuals, -13HU for normal weight individuals, -7HU for overweight individuals, and -16HU for obese individuals. Values below these thresholds indicate a risk of low BMD. This study enriches the Chinese BMD data and offers a swift and effective approach for opportunistically screening low BMD.

Se realizó un estudio sobre la relación entre el valor de la Unidad Hounsfield (HU) de corte único del húmero proximal chino y la densidad mineral ósea (DMO) mediante TC de tórax de rutina y absorciometría de rayos X de energía dual (DEXA). Se recopilaron datos de 240 personas que se sometieron a DEXA y tomografías computarizadas de rutina de tórax (incluidas imágenes completas del húmero proximal) el mismo día en 967 hospitales entre enero de 2019 y diciembre de 2021. El método para medir los valores de HU de un solo corte del húmero proximal en las tomografías computarizadas de tórax mostraron alta confiabilidad y repetibilidad (coeficiente de correlación intraclase > 0,961, P < 0,001). Se observó una fuerte correlación positiva entre los valores de HU de un solo corte del húmero proximal y los resultados de DEXA, demostrando el valor de HU de 20 mm la correlación más alta. En diferentes grupos de IMC, el área bajo la curva (AUC) para el valor HU de 20 mm fue consistentemente el más grande (AUC = 0,701-0,813, P <0,05). Por lo tanto, el valor de HU de 20 mm puede considerarse una referencia fiable para el cribado oportunista de DMO baja, con valores de referencia de -4 HU para personas con bajo peso, -13 HU para personas con peso normal, -7 HU para personas con sobrepeso y -16 HU para personas obesas. Los valores por debajo de estos umbrales indican un riesgo de DMO baja. Este estudio es un aporte para los datos chinos sobre la DMO y ofrece un enfoque rápido y eficaz para detectar de forma oportunista la DMO baja.

Prolonged second stage of labor and risk of postpartum hemorrhage in nullipara with epidural anesthesia and vaginal delivery: A cohort study with propensity score analysis.

OBJECTIVE: To conduct an analysis using propensity score methods, exploring the association between a prolonged second stage (>3 h) and the risk of postpartum hemorrhage (PPH) in a diverse population. METHODS: We conducted a prospective cohort study involving nullipara with epidural anesthesia and vaginal delivery, aged ≥18 years, presenting cephalically, and with a gestational age (GA) of ≥24 weeks at a tertiary maternity hospital in China (chictr.org.cn identifier: ChiCTR2200063094). Women undergoing emergency cesarean section in labor were excluded. The primary outcome was PPH, with secondary outcomes including severe postpartum hemorrhage and blood transfusion. We employed propensity score overlap weighting to analyze the association between prolonged second stage labor and PPH. RESULTS: The study included 3643 nullipara with epidural anesthesia, comprising 77 with a second stage of labor >3 h and 3566 with a second stage ≤3 h. Utilizing propensity score overlap weighting, there were no significant differences observed between the two groups regarding the risk of PPH (29.87% in >3 h group vs 17.64% in ≤3 h group; weighted odds ratio 1.01; 95% CI: 0.51-2.02). Subgroup interaction tests for PPH were not significant for assisted vaginal delivery, induction of labor, macrosomia, third-/fourth-degree perineal laceration, GA >41 weeks, twin pregnancies, episiotomy and GA >37 weeks. Sensitivity analysis did not reveal significant differences. CONCLUSION: This study did not find evidence supporting an increased risk of PPH associated with a second stage of labor lasting >3 h in our population, providing additional evidence for clinical practice.

Peptide hydrogel based electrochemical biosensor for simultaneous monitoring of H2O2 and NO released from three-dimensional cultured breast cancer cells.

An antifouling peptide hydrogel-based electrochemical biosensor was developed for real-time monitoring of hydrogen peroxide (H2O2) and nitric oxide (NO) released by 3D cultured breast cancer cells upon drug stimulation. Platinum nanoparticles (Pt NPs) were electrodeposited on titanium mesh (Pt NPs/TM) to enhance sensitivity and shown to possess excellent electrocatalytic ability toward H2O2 and NO. The composite hydrogel formed by co-assembling of N-fluorenylmethoxycarbonyl diphenylalanine (Fmoc-FF) and a fluorine methoxycarbonyl group-functionalized Lys-(Fmoc)-Asp was coated on Pt NPs/TM electrode surface to provide cellular scaffolding. Their favorable biocompatibility promoted cell adhesion and growth, while good hydrophilicity endowed the sensor with greatly enhanced antifouling capability in complex cell culture environments. The biosensor successfully determined H2O2 and NO secretion from both non-metastatic and metastatic breast cancer cells in real time. Our results demonstrated robust associations between reactive oxygen species (ROS) and reactive nitrogen species (RNS) production and cell malignancy, with the main difference in oxidative stress between the two subtypes of cells being NO release, particularly emphasizing RNS's critical leading in driving cancer metastasis and invasion progression. This sensor holds great potential for cell-release research under the in vivo-like microenvironment and could reveal RNS as an attractive therapeutic target for treating breast cancer.

SUMO E3 ligase MUL1 inhibits lymph node metastasis of bladder cancer by mediating mitochondrial HSPA9 translocation.

Lymph node (LN) metastasis is the dominant cause of death in bladder cancer (BCa) patients, but the underlying mechanism remains largely unknown. In recent years, accumulating studies have confirmed that bidirectional mitochondria-nucleus communication is essential for sustaining multiple function of mitochondria. However, little has been studied regarding whether and how the translocation of mitochondrial proteins is involved in LN metastasis. In this study, we first identified that the SUMO E3 ligase MUL1 was significantly downregulated in LN-metastatic BCa tissues and correlated with a good prognosis. Mechanistically, MUL1 SUMOylated HSPA9 at the K612 residue, leading to HSPA9 export from mitochondria and interaction with SUZ12 and in the nucleus. Consequently, MUL1 induced the ubiquitination-mediated degradation of SUZ12 and EZH2 and induced downstream STAT3 pathway inhibition in a HSPA9-dependent manner. Importantly, mutation of HSPA9 SUMO-conjugation motifs limited the translocation of mitochondrial HSPA9 and blocked the HSPA9-SUZ12 and HSPA9-EZH2 interactions. With mutation of the HSPA9 K612 site, the suppressive role of MUL1 overexpression was lost in BCa cells. Further in vitro and in vivo assays revealed that MUL1 inhibits the metastasis and proliferation of BCa cells. Overall, our study reveals a novel function and molecular mechanism of SUMO E3 ligases in LN metastasis.

Heterotopic pancreas in the gallbladder: A case report.

BACKGROUND: Heterotopic pancreas (HP) refers to pancreatic tissue located in areas with no vascular or anatomical connection to the pancreas. HP occurs mostly in the stomach, duodenum, and colon, and rarely in the gallbladder. CASE SUMMARY: A 57-year-old woman was referred to our hospital complaining of right upper quadrant discomfort for 3 years. An abdominal computed tomography scan revealed adenomyomatosis with a thickened fundus of the gallbladder. The patient underwent a laparoscopic cholecystectomy, and pathological examination unexpectedly showed heterotopic pancreatic tissue in the gallbladder. The patient had a favorable recovery and was discharged on postoperative day 3. She did not report any symptoms or complications at the 6-mo postoperative follow-up. Pathologists should pay close attention to such pancreatic tissue and carefully examine it for dysplasia or malignancy. CONCLUSION: This case provides more information about HP in the gallbladder, a rare occurrence.

Research progress on miR-124-3p in the field of kidney disease.

MicroRNAs (miRNAs) are 18-25 nucleotides long, single-stranded, non-coding RNA molecules that regulate gene expression. They play a crucial role in maintaining normal cellular functions and homeostasis in organisms. Studies have shown that miR-124-3p is highly expressed in brain tissue and plays a significant role in nervous system development. It is also described as a tumor suppressor, regulating biological processes like cancer cell proliferation, apoptosis, migration, and invasion by controlling multiple downstream target genes. miR-124-3p has been found to be involved in the progression of various kidney diseases, including diabetic kidney disease, calcium oxalate kidney stones, acute kidney injury, lupus nephritis, and renal interstitial fibrosis. It mediates these processes through mechanisms like oxidative stress, inflammation, autophagy, and ferroptosis. To lay the foundation for future therapeutic strategies, this research group reviewed recent studies on the functional roles of miR-124-3p in renal diseases and the regulation of its downstream target genes. Additionally, the feasibility, limitations, and potential application of miR-124-3p as a diagnostic biomarker and therapeutic target were thoroughly investigated.

Artemisitene shows superiority over artemisinin in preventing Schistosoma japonica-induced liver disease.

BACKGROUND: Artemisinin (ART) analogs, such as dihydroartemisinin, arteether, artemether, and artesunate, all featuring an endoperoxide bridge, have demonstrated efficacy against schistosomiasis. Artemisitene (ATT), which contains an additional α, ß-unsaturated carbonyl structure, has shown enhanced biological activities. This study aims to evaluate the anti-schistosomaiasis japonica activity of ATT and compare it with ART. METHODS: We assessed liver inflammation and fibrosis in mice using hematoxylin and eosin staining and Sirius red staining, respectively. RNA sequencing analyzed transcriptomics in female and male Schistosoma japonicum (S. japonicum) adult worms and mice livers, with cytokine profiling and flow cytometry to study immune responses under ART or ATT treatment. RESULTS: ATT exhibits a marked reduction in female S. japonicum adult worms and egg numbers, damaging the adult worms' surface. It also influences the transcription of genes related to cellular anatomical structures. Notably, ATT treatment resulted in significant reductions in liver granuloma size and collagen area, alongside lowering serum levels of glutamic pyruvic and glutamic oxaloacetic transaminase more effectively than ART. Both ART and ATT markedly decreased neutrophil frequency in the liver and elevated eosinophil counts. However, only ATT treatment significantly reduced the M1/M2 and Th1/Th2 indices, indicating a pronounced shift in immune response profiles. ATT-affected host immunity correlated with the extent of liver fibrosis and the count of single males more strongly than ART. CONCLUSION: ATT, as a novel preventive strategy for schistosomiasis japonica in mice, significantly outperforms ART.