Application of galactosylated albumin for targeted delivery of triptolide to suppress hepatocellular carcinoma progression through inhibiting de novo lipogenesis.

Hepatocellular carcinoma (HCC) remains the fourth leading cause of cancer-associated death globally with a lack of efficient therapy. The pathogenesis of HCC is a complex and multistep process, highly reliant on de novo lipogenesis, from which tumor cells can incorporate fatty acids to satisfy the necessary energy demands of rapid proliferation and provide survival advantages. Triptolide (TP) is a bioactive ingredient exhibiting potent abilities of anti-proliferation and lipid metabolism regulation, but its clinical application is constrained because of its toxicity and non-specific distribution. The present study has developed galactosylated bovine serum albumin nanoparticles loaded with TP (Gal-BSA-TP NPs) to alleviate systemic toxicity and increase tumor-targeting and antitumor efficacy. Furthermore, Gal-BSA-TP NPs could inhibit de novo lipogenesis via the p53-SREBP1C-FASN pathway to deprive the fuel supply of HCC, offering a specific strategy for HCC treatment. In general, this study provided a biocompatible delivery platform for targeted therapy for HCC from the perspective of de novo lipogenesis.

USP33 facilitates the ovarian cancer progression via deubiquitinating and stabilizing CBX2.

Post-translational modifications of proteins play a pivotal role in both the initiation and progression of ovarian cancer. Despite the recognition of USP33 as a significant factor in various cancers, its specific function and underlying mechanisms in ovarian cancer remain elusive. Proteomics and ubiquitinomics approaches were coupled to screen novel substrate proteins directly regulated by USP33. Our findings unveil that USP33 was observed to eliminate K27- and K48-linked ubiquitin chains from CBX2 at the K277 position. Notably, acetylation of CBX2 at K199, catalyzed by lysine acetyltransferase GCN5, was found to enhance its interaction with USP33, subsequently promoting further deubiquitination and stabilization. Functionally, our experiments demonstrate that USP33 significantly enhances ovarian cancer proliferation and metastasis in a CBX2-dependent manner. Furthermore, analysis revealed a direct positive correlation between the expression levels of USP33 and CBX2 proteins in human specimens, with elevated levels being associated with reduced survival rates in ovarian cancer patients. These findings elucidate the mechanism by which USP33 augments ovarian cancer progression through the stabilization of CBX2, underscoring the USP33-CBX2 axis as a promising therapeutic target in ovarian cancer management.

Involvement of basolateral amygdala-rostral anterior cingulate cortex in mechanical allodynia and anxiety-like behaviors and potential mechanisms of electroacupuncture.

AIMS: Chronic pain is highly associated with anxiety. Electroacupuncture (EA) is effective in relieving pain and anxiety. Currently, little is known about the neural mechanisms underlying the comorbidity of chronic pain and anxiety and the EA mechanism. This study investigated a potential neural circuit underlying the comorbid and EA mechanisms. METHODS: Spared nerve injury (SNI) surgery established the chronic neuropathic pain mouse model. The neural circuit was activated or inhibited using the chemogenetic method to explore the relationship between the neural circuit and mechanical allodynia and anxiety-like behaviors. EA combined with the chemogenetic method was used to explore whether the effects of EA were related to this neural circuit. RESULTS: EA attenuated mechanical allodynia and anxiety-like behaviors in SNI mice, which may be associated with the activity of CaMKII neurons in the basolateral amygdala (BLA). Inhibition of BLACaMKII-rACC induced mechanical allodynia and anxiety-like behaviors in sham mice. Activation of the BLACaMKII-rACC alleviated neuropathic pain and anxiety-like behaviors in SNI mice. The analgesic and anxiolytic effects of 2 Hz EA were antagonized by the inhibition of the BLACaMKII-rACC. CONCLUSION: BLACaMKII-rACC mediates mechanical allodynia and anxiety-like behaviors. The analgesic and anxiolytic effects of 2 Hz EA may be associated with the BLACaMKII-rACC.

Paclitaxel-Induced Hepatotoxicity in Ovarian Cancer Patients: A Case Report.

Paclitaxel plus carboplatin is the most common regimen for the treatment of ovarian cancer. While generally effective, these chemotherapy agents can cause adverse events such as myelotoxicity, nausea, vomiting, and rarely, hepatotoxicity. Paclitaxel is associated with mild elevations in serum aminotransferase levels, but significant hepatotoxicity is uncommon, particularly in patients without prior liver disease. We present a patient with ovarian cancer who developed significant elevation of serum aminotransferases up to 12 times the upper limit of normal after the first cycle of paclitaxel plus carboplatin chemotherapy. Extensive evaluations excluded other potential causes of liver injury and the diagnosis of paclitaxel-induced liver injury was confirmed. The patient was treated with liver protective medications and a reduced dose of paclitaxel (135 mg/m2) for subsequent cycles. Her liver function tests stabilized within 2 to 3 times the upper limit of normal, allowing continuation of chemotherapy and achieving a favorable outcome.

Zinc finger protein LjRSDL regulates arbuscule degeneration of arbuscular mycorrhizal fungi in Lotus japonicus.

In arbuscular mycorrhizal (AM) symbiosis, appropriate regulation of the formation, maintenance, and degeneration of the arbuscule are essential for plants and fungi. In this study, we identified a Cysteine-2/Histidine-2 zinc finger protein (C2H2-ZFP)-encoding gene in Lotus japonicus named Regulator of Symbiosome Differentiation-Like (LjRSDL) that is required for arbuscule degeneration. Evolutionary analysis showed that homologs of LjRSDL exist in mycorrhizal flowering plants. We obtained ProLjRSDL::GUS transgenic hairy roots and showed that LjRSDL was strongly upregulated upon AM colonization, particularly at 18 days post AM fungi inoculation and specifically expressed in arbuscular-containing cells. The mycorrhization rate increased in the ljrsdl mutant but decreased in LjRSDL overexpressed L. japonicus. Interestingly, we observed higher proportions of large arbuscule in the ljrsdl mutant but lower proportions of larger arbuscule in LjRSDL overexpressing plants. Transcriptome analyses indicated that genes involved in arbuscule degeneration were significantly changed upon the dysregulation of LjRSDL and that LjRSDL-dependent regulation in AM symbiosis is mainly via the hormone signal transduction pathway. LjRSDL, therefore, represents a C2H2-ZFP that negatively regulates AM symbiosis. Our study provides insight into understanding plant-AM fungal communication and AM symbiosis development.

A post-marketing study to evaluate the safety and immunogenicity of a quadrivalent influenza split-virion vaccine in elderly people aged 60 years and older.

BACKGROUND: Influenza remains a global public health concern. Understanding the vaccination-induced response in an aging population, which is susceptible and at high risk, is essential for disease prevention and control. Here, we report findings on the safety and immunogenicity of a quadrivalent influenza split-virion vaccine (15 µg/subtype/0.5 ml/dose) (hereinafter referred to as the "quadrivalent influenza vaccine") in a population aged ≥ 60 years. METHODS: This open-label, pragmatic post-marketing trial enrolled 1399 older adults to receive one dose of an approved commercially available quadrivalent influenza vaccine manufactured by Hualan Biological Bacterin Inc. (hereinafter referred to as "Hualan Bio"). Participants with contraindications for the vaccine were excluded, while poor health condition was acceptable. All vaccinated subjects experienced adverse events collection within 30 days and serious adverse events within 180 days post-vaccination. 25% subjects, selected randomly, underwent venous blood sampling pre-vaccination and 30 days after post-vaccination, for detecting antibody titers against each subtype of influenza virus by hemagglutination inhibition assay. The incidences of adverse events and antibody titers against each subtype of influenza virus were statistically analyzed using SAS 9.4. RESULTS: No grade 3 adverse reactions occurred within 30 days post-vaccination. The incidences of overall adverse reactions, local adverse reactions and systemic adverse reactions were 3.79%, 2.86% and 1.00%, respectively. No serious adverse reactions occurred within 180 days post-vaccination. There were 350 subjects who completed venous blood sampling pre-vaccination, among whom 348 subjects completed venous blood sampling at 30 days post-vaccination for immunogenicity assessment. With respect to hemagglutination inhibition antibodies against influenza viruses H1N1, H3N2, BV and BY subtypes, at 30 days post-vaccination, the seroconversion rates were 87.64%, 75.57%, 73.28% and 78.74%, respectively; the seropositive rates were 93.97%, 98.56%, 79.31% and 95.40%, respectively; and the geometric mean increase (GMI) in post-immunization/pre-immunization antibodies was 24.80, 7.26, 10.39 and 7.39, respectively. CONCLUSION: One 15 µg/subtype dose of the vaccine had a good safety profile and elicited favorable immunogenicity among subjects aged ≥ 60 years. The results of this study indicate that Hualan Bio quadrivalent influenza vaccine strike balance between safety and immunogenicity, supporting unnecessity to increase dosage or inoculation frequency for further enhancing immunogenicity. TRIAL REGISTRATION: Registered on ClinicalTrials.gov. REGISTRATION NUMBER: NCT06334510. Registered on 28/03/2024 (retrospectively registered).

DDX5 promotes esophageal squamous cell carcinoma growth through sustaining VAV3 mRNA stability.

Novel therapeutic targets and their inhibitors for esophageal squamous cell carcinoma (ESCC) prevention and therapy are urgently needed. This study aimed to investigate the function of DEAD-box helicase 5 (DDX5) in ESCC progression and to identify a promising inhibitor of DDX5. We verified that DDX5 was highly expressed in ESCC and played an oncogenic role, binding with vav guanine nucleotide exchange factor 3 (VAV3) mRNA and facilitating VAV3 mRNA N6-methyladenosine (m6A) modification by interacting with the m6A methyltransferase 3 (METTL3). M6A-modified VAV3 mRNA was identified by insulin-like growth factor 1 (IGF2BP1), increasing mRNA stability. Methylnissolin-3-ß-D-O-glucoside (MD) inhibited ESCC progression through the DDX5-VAV3 axis. Our findings suggest that DDX5 promotes ESCC progression. MD inhibits ESCC progression by targeting DDX5.

Feasibility and safety of endoscopic full-thickness resection for submucosal tumors in the upper gastrointestinal tract, including predominantly extraluminal submucosal tumors (with video).

OBJECTIVES: Endoscopic full-thickness resection (EFTR) for submucosal tumors (SMTs) has been technically challenging. This retrospective study aimed to evaluate the feasibility, safety, and efficacy of EFTR for upper gastrointestinal (GI) SMTs, including extraluminal lesions. METHODS: We retrospectively investigated 232 patients with SMTs who underwent EFTR from January 2014 to August 2023. Clinicopathologic characteristics, procedure-related parameters, adverse events (AEs), and follow-up outcomes were assessed in all patients. RESULTS: The en-bloc resection and en-bloc with R0 resection rates were 98.7% and 96.1%, respectively. The average endoscopic tumor size measured 17.2 ± 8.7 mm, ranging from 6 to 50 mm. The resection time and suture time were 49.0 ± 19.4 min and 22.5 ± 11.6 min, respectively. In all, 39 lesions (16.8%) exhibited predominantly extraluminal growth. Gastrointestinal stromal tumors (GISTs) were the predominant pathology, accounting for 78.4% of the cases. Twenty-one patients (9.1%) encountered complications, including pneumothorax (1/232, 0.43%), hydrothorax (1/232, 0.43%), localized peritonitis (3/232, 1.29%), and fever (16/232, 6.9%). Although the incidence of postoperative fever was notably higher in the predominantly extraluminal group (7/39, 17.9%) compared to the predominantly intraluminal group (9/193, 4.7%, P = 0.008), there were no significant differences in outcomes of the EFTR procedure. No instances of recurrence were observed during the mean follow-up period of 3.7 ± 2.3 years. CONCLUSION: EFTR was found to be feasible, safe, and effective for resecting upper GI SMTs, including lesions with predominantly extraluminal growth. Further validation in a prospective study is warranted.

Inhibition of TFEB deacetylation in proximal tubular epithelial cells (TECs) promotes TFEB activation and alleviates TEC damage in diabetic kidney disease.

The inhibition of the autophagolysosomal pathway mediated by transcription factor EB (TFEB) inactivation in proximal tubular epithelial cells (TECs) is a key mechanism of TEC injury in diabetic kidney disease (DKD). Acetylation is a novel mechanism that regulates TFEB activity. However, there are currently no studies on whether the adjustment of the acetylation level of TFEB can reduce the damage of diabetic TECs. In this study, we investigated the effect of Trichostatin A (TSA), a typical deacetylase inhibitor, on TFEB activity and damage to TECs in both in vivo and in vitro models of DKD. Here, we show that TSA treatment can alleviate the pathological damage of glomeruli and renal tubules and delay the DKD progression in db/db mice, which is associated with the increased expression of TFEB and its downstream genes. In vitro studies further confirmed that TSA treatment can upregulate the acetylation level of TFEB, promote its nuclear translocation, and activate the expression of its downstream genes, thereby reducing the apoptosis level of TECs. TFEB deletion or HDAC6 knockdown in TECs can counteract the activation effect of TSA on autophagolysosomal pathway. We also found that TFEB enhances the transcription of Tfeb through binding to its promoter and promotes its own expression. Our results, thus, provide a novel therapeutic mechanism for DKD that the alleviation of TEC damage by activating the autophagic lysosomal pathway through upregulating TFEB acetylation can, thus, delay DKD progression.

Tumor cavitation in patients with non-small-cell lung cancer receiving anti-angiogenic therapy with apatinib.

Background: Cavities have been reported in approximately 20% of lung cancer after anti-angiogenesis treatments. However, the effect of which on treatment outcomes remains unclear. This study sought to investigate the incidence and radiographic patterns of tumor cavitation in patients with non-small cell lung cancer (NSCLC) treated with apatinib, and its associations with patients' clinical characteristics and outcomes. Methods: A total of 300 patients with NSCLC treated with apatinib were retrospectively identified. Baseline and follow-up chest computed tomography scans were reviewed to identify tumor cavitation, and the subsequent filling-in of the cavitation. A multivariate logistic regression analysis was conducted to identify the factors associated with tumor cavitation. Survival curves were constructed using the Kaplan-Meier method and compared using the log-rank test. Results: Of the 300 patients, 51 (17.0%) developed lung cavitation after initiating apatinib therapy. The results of the multivariate analysis showed that apatinib combination therapy (vs. apatinib monotherapy, odds ratio: 0.593, 95% confidence interval: 0.412-0.854, P=0.005) was significantly associated with tumor cavitation. Patients with tumor cavitation had significantly longer progression-free survival (PFS) than those without cavitation (8.2 vs. 5.2 months, P<0.01). Of the patients, 18 had cavity filling after progression, while 13 had persistent cavities after progression. The corresponding median PFS times were 11.9 and 3.2 months in patients with filled and persistent cavities after disease progression, respectively (P<0.001). Conclusions: Tumor cavitation occurred in 17% of the NSCLC patients treated with apatinib and was associated with better PFS. Patients who had cavities filled after progression had a better prognosis than those with persistent cavities.

Nine-grid Area Division Method: A New Ideal Bone Puncture Region for Percutaneous Vertebroplasty in Lumbar Spine.

Percutaneous vertebroplasty (PVP) is widely recognized as an efficacious intervention for alleviating low back pain resulting from osteoporotic vertebral compression fractures. The ideal bone puncture point is conventionally situated at the projection "left 10 points, right 2 points" of the pedicle in the lumbar spine. Determining the optimal bone puncture point represents a critical and complex challenge. The accuracy of percutaneous vertebroplasty (PVP) is primarily influenced by the proficiency of the operating surgeons and the utilization of multiple fluoroscopes during the conventional procedure. Incidences of puncture-related complications have been documented globally. In an effort to enhance the precision of the surgical technique and reduce the occurrence of puncture-related complications, our team applied the "Nine-grid Area Division Method" for PVP in the lumbar spine to modify the traditional procedure. There is potential to decrease the number of puncture times, the radiation exposure dosage, and the duration of surgical procedures. This protocol introduces the definition of the "Nine-grid Area Division Method" and describes the process of modeling target vertebrae DICOM imaging data within medical imaging processing software, simulating operations within a 3-D model, refining the 3-D model using reverse engineering production software, reconstructing the vertebral engineering model within 3-D modeling design software, and utilizing surgical data to determine safe entry regions for pedicle projection. By employing this methodology, surgeons can effectively identify appropriate puncture points with precision and ease, thereby reducing the intricacies associated with puncturing and enhancing the overall accuracy of surgical procedures.

[Surgical technique and effect of the pulsatile tinnitus associated with sigmoid sinus on the dominant side of reflux].

Objective:To explore the effect of surgical treatment of the pulsatile tinnitus associated with sigmoid sinus on the dominant side of reflux. Methods:The clinical data of 43 patients with reflux dominant side pulsating tinnitus admitted by the same doctor from 2017 to 2023 were retrospectively studied to observe the curative effect of surgical treatment. Operation method: The sound insulation barrier was established by repair technique of bone wall defect of sigmoid sinus with "capping method", without changing the blood flow and blood vessel wall of sigmoid sinus. Results:No surgical complications occurred in all patients. During the follow-up period of 3 months to 6.9 years, 14 patients（32.6%） were cured, 18 patients（41.9%） were significantly effective, 4 patients（9.3%） were effective, and 7 patients（16.3%） were ineffective. The difference of tinnitus grade before and after surgery was statistically significant. Conclusion:In this group of cases, the sound insulation barrier was established by "capping method" technique of repairing bone wall defect of sigmoid sinus, which effectively avoided the disturbance of hemorheology status and vascular wall, thus avoiding the risk of venous wall stenosis and thrombosis on the dominant reflux side. The surgical method was easy to master, and the curative effect was significant, which was worthy of clinical promotion.

Agonist Discovery for Membrane Proteins on Live Cells by Using DNA-encoded Libraries.

Identifying biologically active ligands for membrane proteins is an important task in chemical biology. We report an approach to directly identify small molecule agonists against membrane proteins by selecting DNA-encoded libraries (DELs) on live cells. This method connects extracellular ligand binding with intracellular biochemical transformation, thereby biasing the selection toward agonist identification. We have demonstrated the methodology with three membrane proteins: epidermal growth factor receptor (EGFR), thrombopoietin receptor (TPOR), and insulin receptor (INSR). A ∼30 million and a 1.033 billion-compound DEL were selected against these targets, and novel agonists with subnanomolar affinity and low micromolar cellular activities have been discovered. The INSR agonists activated the receptor by possibly binding to an allosteric site, exhibited clear synergistic effects with insulin, and activated the downstream signaling pathways. Notably, the agonists did not activate the insulin-like growth factor 1 receptor (IGF-1R), a highly homologous receptor whose activation may lead to tumor progression. Collectively, this work has developed an approach toward "functional" DEL selections on the cell surface and may provide a widely applicable method for agonist discovery for membrane proteins.

A promising anti-tumor targeting on ERMMDs mediated abnormal lipid metabolism in tumor cells.

The investigation of aberrations in lipid metabolism within tumor has become a burgeoning field of study that has garnered significant attention in recent years. Lipids can serve as a potent source of highly energetic fuel to support the rapid growth of neoplasia, in where the ER-mitochondrial membrane domains (ERMMDs) provide an interactive network for facilitating communication between ER and mitochondria as well as their intermembrane space and adjunctive proteins. In this review, we discuss fatty acids (FAs) anabolic and catabolic metabolism, as well as how CPT1A-VDAC-ACSL clusters on ERMMDs participate in FAs transport, with a major focus on ERMMDs mediated collaborative loop of FAO, Ca2+ transmission in TCA cycle and OXPHOS process. Here, we present a comprehensive perspective on the regulation of aberrant lipid metabolism through ERMMDs conducted tumor physiology might be a promising and potential target for tumor starvation therapy.

Integrating Complaint Analysis into Hospital Management: A Comparative Study of Surgical and Non-Surgical Complaints.

Aims/Background: In an era where patient-centred care is paramount, effectively managing and analyzing hospital complaints is crucial for improving service quality and patient satisfaction. This study examines hospital complaints to enhance management practices by differentiating between surgery-related and non-surgery-related grievances. By identifying patterns in complaint types and outcomes, we aim to inform targeted quality improvement strategies that address specific patient concerns and boost operational efficiency. Methods: The study utilized data from an internal complaint management system over one year. Complaints were categorized as either surgery-related or non-surgery-related. Descriptive statistics and cross-tabulation analysis were employed to examine the data. The sample comprised 132 complaints, with 67 being surgery-related and 65 non-surgery-related. Results: The analysis revealed that surgery-related complaints frequently involved issues with 'Patient Communication' and 'Surgical Error', while non-surgery-related complaints were primarily about the 'Medical Treatment Process'. The Surgery Department received the highest number of complaints, indicating a critical area for intervention. Additionally, the correlation between complaint types and outcomes provided insights into potential areas for improvement. Conclusion: The findings highlight the need for targeted communication training and procedural enhancements in surgical departments. Non-surgical departments should focus on improving treatment protocols and transparency. These strategies can reduce complaints and improve patient satisfaction. Future research should develop and test interventions based on these insights to further enhance healthcare quality.

Unlocking the potential of rice bran oil body as fat replacement in cookies: single and double crosslinked binary emulsion-filled gels based on lutein-loaded rice bran oil body emulsion.

BACKGROUND: Rice bran oil body is rich in nutritional value, which is a byproduct of rice processing. The aim of this study is to develop a novel emulsion-filled gel with lutein-loaded rice bran oil body and investigate its functionality as a fat replacer in cookies. The effects of incorporating structured oil body in the form of emulsion-filled gel instead of butter in cookies with a ratio of 0, 10, 20 and 50 wt% formulation were determined by measuring appearance, texture, thermodynamic properties, moisture distribution and microstructure. RESULTS: The results demonstrated the relationship between geometry, moisture and structure. The 20 wt% emulsion-filled gel substitution ratio yielded mobility and distribution abilities of melted fat and sugar in the cookies that were closest to those of butter. The addition of emulsion-filled gel increased the L* value and decreased the a* value, while the b* value of the cookie increased due to the advanced delivery of lutein by oil body. By controlling the addition ratio, the texture of the cookies can be adjusted. Starch granules were separated due to colloidal particles, reducing saturated fat content and decreasing cookie gelatinization enthalpy. The fat coating on starch particles enhanced the binding capacity of free water, improving air entrapment and forming a constrained gluten network structure. CONCLUSION: These findings provide a theoretical basis for rice bran oil body as a novel substitute for butter in the development of healthy, high-quality cookies. © 2024 Society of Chemical Industry.

Defective autophagy of pericytes enhances radiation-induced senescence promoting radiation brain injury.

BACKGROUND: Radiation-induced brain injury (RBI) represents a major challenge for cancer patients undergoing cranial radiotherapy. However, the molecular mechanisms and therapeutic strategies of RBI remain inconclusive. With the continuous exploration of the mechanisms of RBI, an increasing number of studies have implicated cerebrovascular dysfunction as a key factor in RBI-related cognitive impairment. As pericytes are a component of the neurovascular unit, there is still a lack of understanding in current research about the specific role and function of pericytes in RBI. METHODS: We constructed a mouse model of RBI-associated cognitive dysfunction in vivo and an in vitro radiation-induced pericyte model to explore the effects of senescent pericytes on the blood-brain barrier and normal CNS cells, even glioma cells. To further clarify the effects of pericyte autophagy on senescence, molecular mechanisms were explored at the animal and cellular levels. Finally, we validated the clearance of pericyte senescence by using senolytic drug and all-trans retinoic acid to investigate the role of radiation-induced pericyte senescence. RESULTS: Our findings indicated that radiation-induced pericyte senescence plays a key role in blood-brain barrier dysfunction, leading to RBI and subsequent cognitive decline. Strikingly, pericyte senescence also contributes to the growth and invasion of glioma cells. We further demonstrate that defective autophagy in pericytes is a vital regulatory mechanism for pericyte senescence. Moreover, autophagy activated by rapamycin can reverse pericyte senescence. Notably, the elimination of senescent cells by senolytic drugs significantly mitigated radiation-induced cognitive dysfunction. DISSCUSSION: Our results demonstrated that pericyte senescence may be a promising therapeutic target for RBI and glioma progression.

Epithelial-mesenchymal plasticity in cancer: signaling pathways and therapeutic targets.

Currently, cancer is still a leading cause of human death globally. Tumor deterioration comprises multiple events including metastasis, therapeutic resistance and immune evasion, all of which are tightly related to the phenotypic plasticity especially epithelial-mesenchymal plasticity (EMP). Tumor cells with EMP are manifest in three states as epithelial-mesenchymal transition (EMT), partial EMT, and mesenchymal-epithelial transition, which orchestrate the phenotypic switch and heterogeneity of tumor cells via transcriptional regulation and a series of signaling pathways, including transforming growth factor-ß, Wnt/ß-catenin, and Notch. However, due to the complicated nature of EMP, the diverse process of EMP is still not fully understood. In this review, we systematically conclude the biological background, regulating mechanisms of EMP as well as the role of EMP in therapy response. We also summarize a range of small molecule inhibitors, immune-related therapeutic approaches, and combination therapies that have been developed to target EMP for the outstanding role of EMP-driven tumor deterioration. Additionally, we explore the potential technique for EMP-based tumor mechanistic investigation and therapeutic research, which may burst vigorous prospects. Overall, we elucidate the multifaceted aspects of EMP in tumor progression and suggest a promising direction of cancer treatment based on targeting EMP.

Barriers and facilitators of screening postpartum depression by primary maternal health workers: A mixed methods study based on the normalization process theory.

BACKGROUND: Postpartum depression (PPD) significantly impacts mothers and children's health. China aims to incorporate PPD screening in postpartum home visits, but research on implementation barriers and facilitators is scarce. We designed and implemented a new PPD screening program in Changsha, China, requiring maternal health workers to integrate PPD screening into their postpartum home visits. AIMS: To identify real-world barriers and facilitators associated with integrating PPD screening into routine home visits from the perspective of maternal health workers. METHODS: We employed a mixed-methods approach. Maternal health workers involved in the newly introduced PPD screening program were included. Guided by Normalization Process Theory (NPT), quantitative data were collected using the NoMAD instrument, and qualitative data were obtained through semi-structured interviews. Data were analyzed using descriptive statistics for the survey and thematic analysis for the interviews. RESULTS: All 42 maternal health workers involved in the new PPD program completed the quantitative survey, and nine participated in qualitative interviews. The NoMAD survey revealed high scores for Coherence and Cognitive Participation, but lower scores for Collective Action, particularly regarding insufficient skills and resource adequacy. Thematic analysis identified several barriers, including workload concerns, the need for enhanced psychological healthcare capacity, and lack of economic incentives. Facilitators included the integration of structured feedback and clear referral pathways. CONCLUSION: Addressing identified barriers through targeted skill training, well-defined referral pathways, and formal recognition of the screening program in performance evaluations could help achieve successful normalization.

Crosstalk between epitranscriptomic and epigenomic modifications and its implication in human diseases.

Crosstalk between N6-methyladenosine (m6A) and epigenomes is crucial for gene regulation, but its regulatory directionality and disease significance remain unclear. Here, we utilize quantitative trait loci (QTLs) as genetic instruments to delineate directional maps of crosstalk between m6A and two epigenomic traits, DNA methylation (DNAme) and H3K27ac. We identify 47 m6A-to-H3K27ac and 4,733 m6A-to-DNAme and, in the reverse direction, 106 H3K27ac-to-m6A and 61,775 DNAme-to-m6A regulatory loci, with differential genomic location preference observed for different regulatory directions. Integrating these maps with complex diseases, we prioritize 20 genome-wide association study (GWAS) loci for neuroticism, depression, and narcolepsy in brain; 1,767 variants for asthma and expiratory flow traits in lung; and 249 for coronary artery disease, blood pressure, and pulse rate in muscle. This study establishes disease regulatory paths, such as rs3768410-DNAme-m6A-asthma and rs56104944-m6A-DNAme-hypertension, uncovering locus-specific crosstalk between m6A and epigenomic layers and offering insights into regulatory circuits underlying human diseases.