ZNF197-AS1/miR-425/GABARAPL1 Axis: A Novel Regulatory Mechanism in Uveal Melanoma.

This study investigates the role of the long non-coding RNA (lncRNA) ZNF197-AS1 in uveal melanoma (UM), focusing on its function within a competing endogenous RNA (ceRNA) network. Utilizing the UM-related TCGA dataset, we analyzed the expression levels of ZNF197-AS1 and its correlation with miR-425 and GABARAPL1, an essential autophagy-related gene. Our analysis revealed that ZNF197-AS1 acts as a ceRNA by competitively binding to miR-425, resulting in the upregulation of GABARAPL1. This interaction plays a crucial role in the growth and metastasis of UM. The expression of GABARAPL1 showed a strong correlation with the clinical outcomes of UM patients. Furthermore, in vitro assays confirmed that ZNF197-AS1 impedes UM cell proliferation, migration, and invasion by modulating the miR-425/GABARAPL1 axis. These findings suggest that ZNF197-AS1 can effectively inhibit UM progression through this ceRNA regulatory network. This study provides valuable insights into the molecular mechanisms underlying UM and highlights the potential of targeting the ZNF197-AS1/miR-425/GABARAPL1 axis as a therapeutic strategy for UM.

Secreted PTEN binds PLXDC2 on macrophages to drive antitumor immunity and tumor suppression.

Loss of phosphatase and tensin homolog (PTEN) has been linked to an immunosuppressive tumor microenvironment, but its underlying mechanisms remain largely enigmatic. Here, we report that PTEN can be secreted by the transmembrane emp24 domain-containing protein 10 (TMED10)-channeled protein secretion pathway. Inhibiting PTEN secretion from tumor cells contributes to immunosuppression and impairs the tumor-suppressive role of PTEN, while intratumoral injection of PTEN protein promotes antitumor immunity and suppresses tumor growth in mice. Mechanistically, extracellular PTEN binds to the plexin domain-containing protein 2 (PLXDC2) on macrophages, triggering subsequent activation of JAK2-STAT1 signaling, which switches tumor-associated macrophages (TAMs) from the immunosuppressive to inflammatory phenotype, leading to enhanced activation of CD8+ T and natural killer cells. Importantly, PTEN treatment also enhances the therapeutic efficacy of anti-PD-1 treatment in mice and reverses the immune-suppressive phenotype of patient-derived primary TAMs. These data identify a cytokine-like role of PTEN in immune activation and tumor suppression and demonstrate the therapeutic potential for extracellular administration of PTEN in cancer immunotherapy.

High-Resolution Magnetic Resonance Angiography of Tumor Vasculatures with an Interlocking Contrast Agent.

The comprehensive evaluation of tumor vasculature that is crucial for the development, expansion, and spread of cancer still remains a great challenge, especially the three-dimensional (3D) evaluation of vasculatures. In this study, we proposed a magnetic resonance (MR) angiography strategy with interlocking stratagem of zwitterionic Gd-chelate contrast agents (PAA-Gd) for continuous monitoring of tumor angiogenesis progression in 3D. Owing to the zwitterionic structure and nanoscale molecular diameter, the longitudinal molar relaxivity (r1) of PAA-Gd was 2.5 times higher than that of individual Gd-chelates on a 7.0 T MRI scanner, resulting in the higher-resolution visualization of tumor vasculatures. More importantly, PAA-Gd has the appropriate blood half-life (69.2 min), emphasizing the extended imaging window compared to the individual Gd-chelates. On this basis, by using PAA-Gd as the contrast agent, the high-resolution, 3D depiction of the spatiotemporal distribution of microvasculature in solid tumors formed by different cell lines over various inoculation times has been obtained. This method offers an effective approach for early tumor diagnosis, development assessment, and prognosis evaluation.

High cardiovascular mortality risk among older merkel cell carcinoma patients.

OBJECTIVE: Previous research has primarily focused on the incidence and mortality rates of Merkel cell carcinoma (MCC), neglecting the examination of cardiovascular mortality (CVM) risk among survivors, particularly older patients. This study aims to assess the risk of CVM in older individuals diagnosed with MCC. METHODS: Data pertaining to older MCC patients were obtained from the Surveillance, Epidemiology, and End Results database (SEER). CVM risk was measured using standardized mortality ratio (SMR) and cumulative mortality. Multivariate Fine-Gray's competing risk model was utilized to evaluate the risk factors contributing to CVM. RESULTS: Among the study population of 2,899 MCC patients, 465 (16.0%) experienced CVM during the follow-up period. With the prolongation of the follow-up duration, the cumulative mortality rate for CVM reached 27.36%, indicating that cardiovascular disease (CVD) became the second most common cause of death. MCC patients exhibited a higher CVM risk compared to the general population (SMR: 1.69; 95% CI: 1.54-1.86, p < 0.05). Notably, the SMR for other diseases of arteries, arterioles, and capillaries displayed the most significant elevation (SMR: 2.69; 95% CI: 1.16-5.29, p < 0.05). Furthermore, age at diagnosis and disease stage were identified as primary risk factors for CVM, whereas undergoing chemotherapy or radiation demonstrated a protective effect. CONCLUSION: This study emphasizes the significance of CVM as a competing cause of death in older individuals with MCC. MCC patients face a heightened risk of CVM compared to the general population. It is crucial to prioritize cardiovascular health starting from the time of diagnosis and implement personalized CVD monitoring and supportive interventions for MCC patients at high risk. These measures are essential for enhancing survival outcomes.

Clinical efficacy and safety of double-channel anastomosis and tubular gastroesophageal anastomosis in gastrectomy.

BACKGROUND: With the continuous progress of surgical technology and improvements in medical standards, the treatment of gastric cancer surgery is also evolving. Proximal gastrectomy is a common treatment, but double-channel anastomosis and tubular gastroesophageal anastomosis have attracted much attention in terms of surgical options. Each of these two surgical methods has advantages and disadvantages, so it is particularly important to compare and analyze their clinical efficacy and safety. AIM: To compare the surgical safety, clinical efficacy, and safety of double-channel anastomosis and tubular gastroesophageal anastomosis in proximal gastrectomy. METHODS: The clinical and follow-up data of 99 patients with proximal gastric cancer who underwent proximal gastrectomy and were admitted to our hospital between January 2018 and September 2023 were included in this retrospective cohort study. According to the different anastomosis methods used, the patients were divided into a double-channel anastomosis group (50 patients) and a tubular gastroesophageal anastomosis group (49 patients). In the double-channel anastomosis, Roux-en-Y anastomosis of the esophagus and jejunum was performed after proximal gastric dissection, and then side-to-side anastomosis was performed between the residual stomach and jejunum to establish an antireflux barrier and reduce postoperative gastroesophageal reflux. In the tubular gastroesophageal anastomosis group, after the proximal end of the stomach was cut, tubular gastroplasty was performed on the distal stump of the stomach and a linear stapler was used to anastomose the posterior wall of the esophagus and the anterior wall of the stomach tube. The main outcome measure was quality of life 1 year after surgery in both groups, and the evaluation criteria were based on the postgastrectomy syndrome assessment scale. The greater the changes in body mass, food intake per meal, meal quality subscale score, and total measures of physical and mental health score, the better the condition; the greater the other indicators, the worse the condition. The secondary outcome measures were intraoperative and postoperative conditions, the incidence of postoperative long-term complications, and changes in nutritional status at 1, 3, 6, and 12 months after surgery. RESULTS: In the double-channel anastomosis cohort, there were 35 males (70%) and 15 females (30%), 33 (66.0%) were under 65 years of age, and 37 (74.0%) had a body mass index ranging from 18 to 25 kg/m2. In the group undergoing tubular gastroesophageal anastomosis, there were eight females (16.3%), 21 (42.9%) individuals were under the age of 65 years, and 34 (69.4%) had a body mass index ranging from 18 to 25 kg/m2. The baseline data did not significantly differ between the two groups (P > 0.05 for all), with the exception of age (P = 0.021). The duration of hospitalization, number of lymph nodes dissected, intraoperative blood loss, and perioperative complication rate did not differ significantly between the two groups (P > 0.05 for all). Patients in the dual-channel anastomosis group scored better on quality of life measures than did those in the tubular gastroesophageal anastomosis group. Specifically, they had lower scores for esophageal reflux [2.8 (2.3, 4.0) vs 4.8 (3.8, 5.0), Z = 3.489, P < 0.001], eating discomfort [2.7 (1.7, 3.0) vs 3.3 (2.7, 4.0), Z = 3.393, P = 0.001], total symptoms [2.3 (1.7, 2.7) vs 2.5 (2.2, 2.9), Z = 2.243, P = 0.025], and other aspects of quality of life. The postoperative symptoms [2.0 (1.0, 3.0) vs 2.0 (2.0, 3.0), Z = 2.127, P = 0.033], meals [2.0 (1.0, 2.0) vs 2.0 (2.0, 3.0), Z = 3.976, P < 0.001], work [1.0 (1.0, 2.0) vs 2.0 (1.0, 2.0), Z = 2.279, P = 0.023], and daily life [1.7 (1.3, 2.0) vs 2.0 (2.0, 2.3), Z = 3.950, P < 0.001] were all better than those of the tubular gastroesophageal anastomosis group. The group that underwent tubular gastroesophageal anastomosis had a superior anal exhaust score [3.0 (2.0, 4.0) vs 3.5 (2.0, 5.0) (Z = 2.345, P = 0.019] compared to the dual-channel anastomosis group. Hemoglobin, serum albumin, total serum protein, and the rate at which body mass decreased one year following surgery did not differ significantly between the two groups (P > 0.05 for all). CONCLUSION: The safety of double-channel anastomosis in proximal gastric cancer surgery is equivalent to that of tubular gastric surgery. Compared with tubular gastric surgery, double-channel anastomosis is a preferred surgical technique for proximal gastric cancer. It offers advantages such as less esophageal reflux and improved quality of life.

Evolution mechanism of microbial community structure and metabolic activity in aquatic nutrient-poor sedimentary environments driven by 17ß-estradiol pollution.

17ß-Estradiol (E2) is a novel micro-pollutant that is widely distributed in aquatic sediments and has a universal toxicological effect on aquatic organisms. However, its ecological impact on aquatic microorganisms is not yet clear. In this study, we designed a simulation system for oligotrophic water deposition in the laboratory, analyzed the impact of different concentrations of E2 pollution on the carbon metabolism activity (carbon gas emission rate) of water microorganisms. Based on high-throughput sequencing results, we revealed the impact of E2 pollution on the community structure succession and metabolic function of bacteria, archaea, and methanogens in the simulated system, explored the impact mechanism of E2 pollution on microbial carbon metabolism in water bodies. Our results suggested that E2 significantly impacts the bacterial and archaeal community rather than the methanogen community, thereby indirectly inhibiting methane production. The achievements will bridge the theoretical gap between estrogen metabolism and carbon metabolism in sedimentary environments and contribute to enriching the ecological toxicology theory of steroid estrogen.

Deciphering the pathogenic role of rare RAF1 heterozygous missense mutation in the late-presenting DDH.

Background: Developmental Dysplasia of the Hip (DDH) is a skeletal disorder where late-presenting forms often escape early diagnosis, leading to limb and pain in adults. The genetic basis of DDH is not fully understood despite known genetic predispositions. Methods: We employed Whole Genome Sequencing (WGS) to explore the genetic factors in late-presenting DDH in two unrelated families, supported by phenotypic analyses and in vitro validation. Results: In both cases, a novel de novo heterozygous missense mutation in RAF1 (c.193A>G [p.Lys65Glu]) was identified. This mutation impacted RAF1 protein structure and function, altering downstream signaling in the Ras/ERK pathway, as demonstrated by bioinformatics, molecular dynamics simulations, and in vitro validations. Conclusion: This study contributes to our understanding of the genetic factors involved in DDH by identifying a novel mutation in RAF1. The identification of the RAF1 mutation suggests a possible involvement of the Ras/ERK pathway in the pathogenesis of late-presenting DDH, indicating its potential role in skeletal development.

Recursive partitioning analysis for survival stratification and early imaging prediction of molecular biomarker in glioma patients.

BACKGROUND: Glioma is the most common primary brain tumor with high mortality and disability rates. Recent studies have highlighted the significant prognostic consequences of subtyping molecular pathological markers using tumor samples, such as IDH, 1p/19q, and TERT. However, the relative importance of individual markers or marker combinations in affecting patient survival remains unclear. Moreover, the high cost and reliance on postoperative tumor samples hinder the widespread use of these molecular markers in clinical practice, particularly during the preoperative period. We aim to identify the most prominent molecular biomarker combination that affects patient survival and develop a preoperative MRI-based predictive model and clinical scoring system for this combination. METHODS: A cohort dataset of 2,879 patients was compiled for survival risk stratification. In a subset of 238 patients, recursive partitioning analysis (RPA) was applied to create a survival subgroup framework based on molecular markers. We then collected MRI data and applied Visually Accessible Rembrandt Images (VASARI) features to construct predictive models and clinical scoring systems. RESULTS: The RPA delineated four survival groups primarily defined by the status of IDH and TERT mutations. Predictive models incorporating VASARI features and clinical data achieved AUC values of 0.85 for IDH and 0.82 for TERT mutations. Nomogram-based scoring systems were also formulated to facilitate clinical application. CONCLUSIONS: The combination of IDH-TERT mutation status alone can identify the most distinct survival differences in glioma patients. The predictive model based on preoperative MRI features, supported by clinical assessments, offers a reliable method for early molecular mutation prediction and constitutes a valuable scoring tool for clinicians in guiding treatment strategies.

Macrophage Membrane-Encapsulated Dopamine-Modified Poly Cyclodextrin Multifunctional Biomimetic Nanoparticles for Atherosclerosis Therapy.

Atherosclerotic plaques exhibit high cholesterol deposition and oxidative stress resulting from high reactive oxygen species (ROS). These are the major components in plaques and the main pro-inflammatory factor. Therefore, it is crucial to develop an effective therapeutic strategy that can simultaneously address the multiple pro-inflammatory factors via removing cholesterol and inhibiting the overaccumulated ROS. In this study, we constructed macrophage membrane-encapsulated biomimetic nanoparticles (MM@DA-pCD@MTX), which not only alleviate cholesterol deposition at the plaque lesion via reverse cholesterol transport but also scavenge the overaccumulated ROS. ß-Cyclodextrin (ß-CD) and the loaded methotrexate (MTX) act synergistically to induce cholesterol efflux for inhibiting the formation of foam cells. Among them, MTX up-regulated the expression of ABCA1, CYP27A1, and SR-B1. ß-CD increased the solubility of cholesterol crystals. In addition, the ROS scavenging property of dopamine (DA) was perfectly preserved in MM@DA-pCD@MTX, which could scavenge the overaccumulated ROS to alleviate the oxidative stress at the plaque lesion. Last but not least, MM-functionalized "homing" targeting of atherosclerotic plaques not only enables the targeted drug delivery but also prolongs in vivo circulation time and drug half-life. In summary, MM@DA-pCD@MTX emerges as a potent, multifunctional therapeutic platform for AS treatment, offering a high degree of biosafety and efficacy in addressing the complex pathophysiology of atherosclerosis.

Development of lignin hydrogel reinforced polypyrrole rich electrode material for supercapacitor and sensing applications.

The preparation of natural polymer-based highly conductive hydrogels with reliable durability for applications in supercapacitors (SCs) is still challenging. Herein, a facile method to prepare alkaline lignin (AL)-based polypyrrole (PPy)-rich, high-conductive PPy@AL/PEGDGE gel was reported, where AL was used as a dopant, polyethylene glycol diglycidyl ether (PEGDGE) as a cross-linking agent, and PPy as a conducting polymer. The PPy@AL/PEGDGE gel electrode materials with hollow structures were prepared by electrochemical deposition and chemical etching method and then assembled into sandwich-shaped SCs. Cyclic voltammetry (CV), galvanotactic charge discharge (GCD), electrochemical impedance spectroscopy (EIS) and cycling stability tests of the PPy@AL/PEGDGE SCs were performed. The results demonstrated that the SCs can achieve a conductivity of 25.9 S·m-1 and a specific capacitance of 175 F·g-1, which was 127.4 % higher compared to pure PPy (77 F·g-1) electrode. The highest energy density and power density for the SCs were obtained at 23.06 Wh·kg-1 and 5376 W·kg-1, respectively. In addition, the cycling performance was also higher than that of pure PPy assembled SCs (50 %), and the capacitance retention rate can reach 72.3 % after 1000 cycles. The electrode materials are expected to be used as sensor and SCs devices.

Salvage of Iatrogenic Sciatic Nerve Injury Caused by Operatively Treated Acetabular Fractures: Two Cases and Literature Review.

BACKGROUND: While sciatic nerve injury has been described as a complication of acetabular fractures, iatrogenic nerve injury remains sparsely reported. This study aims to assess iatrogenic sciatic nerve injuries occurring during acetabular fracture surgery, tracking their neurological recovery and clinical outcomes, and investigating any correlation between recovery and the severity of neurologic injury to facilitate physicians in providing prediction of prognosis. CASE PRESENTATION: We present two cases of male patients, aged 56 and 22, who developed sciatic palsy due to iatrogenic nerve injury during acetabular fracture surgery. Iatrogenic sciatic nerve injury resulted from operatively treated acetabular fractures. Surgical exploration, involving internal fixation removal and nerve decompression, successfully alleviated symptoms in both cases postoperatively. At the latest follow-up, one patient achieved full recovery with excellent function, while the other exhibited residual deficits at the L5/S1 root level along with minimal pain. CONCLUSION: Sciatic nerve injury likely stemmed from reduction techniques and internal fixation procedures for the posterior column, particularly when performed with the hip flexed, thereby placing tension on the sciatic nerve. Our case reports underscore the significance of liberal utilization of electrophysiologic examinations and intraoperative monitoring for the prediction of prognosis. Surgical exploration, encompassing internal fixation removal and nerve decompression, represents an effective intervention for resolving sciatic palsy, encompassing both sensory neuropathy and motor symptoms.

Predicted body fat percentage, fat mass and lean body mass in relation to risk of prostate cancer: Results from the NHANES 1999 to 2010.

The purpose of this study is to examine the relationship between fat mass (FM), body fat percentage (BF%), lean body mass (LM), and prostate cancer (PCa), and evaluate their potential impact on the risk of PCa. Data from the National Health and Nutrition Examination Survey (NHANES) of the United States were utilized. Adult male participants from 6 survey cycles between 1999 and 2010 were selected as the study sample. Multivariable logistic regression analysis was conducted to explore the association between BF%, LM, and PCa, while controlling for potential confounding variables. Among the 8440 participants, 359 cases of PCa were diagnosed. The relationship between BF%, LM, and PCa was nonlinear. In the multivariable logistic regression analysis, there was an independent association between BF% and PCa risk (OR: 1.04, 95% CI: 1.02-1.06), suggesting that higher BF% levels are associated with an increased risk of PCa. Conversely, higher LM levels were associated with a decreased risk of PCa (OR: 0.96, 95% CI: 0.95-0.98). The findings of this study demonstrate a correlation between BF% and LM with PCa, but do not provide direct evidence of a causal relationship. Higher BF% levels are associated with an increased risk of PCa, while higher LM levels are associated with a decreased risk. These results provide valuable insights for understanding and potentially preventing PCa, although further research is needed to fully comprehend the underlying mechanisms.

Analysis of chemoresistance characteristics and prognostic relevance of postoperative gemcitabine adjuvant chemotherapy in pancreatic cancer.

AIM: To investigate the relationship between chemoresistance in pancreatic cancer patients receiving postoperative gemcitabine adjuvant therapy and specific clinical/pathological characteristics, as well as its impact on patient prognosis. METHODS: From June 2018 to June 2021, clinical and pathological data of 148 pancreatic cancer patients were collected, and 101 patients were followed up for tumor recurrence/metastasis and survival status. The correlation between chemoresistance and specific clinical/pathological characteristics or patient prognosis was retrospectively analyzed. RESULTS: Of the 148 patients, 78 were in the chemoresistance group and 70 in the non-chemoresistance group. Univariate analysis showed that the development of chemoresistance may be related to patient age, combined diabetes, preoperative CA19-9 level, tumor size, AJCC stage, vascular invasion, and positive lymph node ratio. Furthermore, subsequent multivariate analysis incorporating these variables indicated that tumor size may be a key factor influencing chemoresistance (p < 0.001, OR = 1.584). Log-rank test showed patients in the chemoresistance group had worse overall survival (OS) (HR = 2.102, p = 0.018) and progression free survival (PFS) (HR = 3.208, p = 0.002) than patients in the non-chemoresistance group; and patients with smaller size tumors (diameter ≤3 cm) had significantly better OS (HR = 2.923, p < 0.001) and PFS (HR = 2.930, p = 0.003) than those with larger size tumors (diameter >3 cm). CONCLUSIONS: Patients with pancreatic cancer receiving postoperative gemcitabine adjuvant therapy are more likely to develop chemoresistance when their tumor sizes are larger (diameter >3 cm). Development of chemoresistance exacerbates the prognosis of patients with pancreatic cancer, and larger tumor size is also a risk factor for poor prognosis in these patients.

The structural basis for 2'-5'/3'-5'-cGAMP synthesis by cGAS.

cGAS activates innate immune responses against cytosolic double-stranded DNA. Here, by determining crystal structures of cGAS at various reaction stages, we report a unifying catalytic mechanism. apo-cGAS assumes an array of inactive conformations and binds NTPs nonproductively. Dimerization-coupled double-stranded DNA-binding then affixes the active site into a rigid lock for productive metal•substrate binding. A web-like network of protein•NTP, intra-NTP, and inter-NTP interactions ensures the stepwise synthesis of 2'-5'/3'-5'-linked cGAMP while discriminating against noncognate NTPs and off-pathway intermediates. One divalent metal is sufficient for productive substrate binding, and capturing the second divalent metal is tightly coupled to nucleotide and linkage specificities, a process which manganese is preferred over magnesium by 100-fold. Additionally, we elucidate how mouse cGAS achieves more stringent NTP and linkage specificities than human cGAS. Together, our results reveal that an adaptable, yet precise lock-and-key-like mechanism underpins cGAS catalysis.

Phytophthora sojae Effector PsAvh113 Targets Transcription Factors in Nicotiana benthamiana.

Phytophthora sojae is a type of pathogenic oomycete that causes Phytophthora root stem rot (PRSR), which can seriously affect the soybean yield and quality. To subvert immunity, P. sojae secretes a large quantity of effectors. However, the molecular mechanisms regulated by most P. sojae effectors, and their host targets remain unexplored. Previous studies have shown that the expression of PsAvh113, an effector secreted by Phytophthora sojae, enhances viral RNA accumulations and symptoms in Nicotiana benthamiana via VIVE assay. In this study, we analyzed RNA-sequencing data based on disease symptoms in N. benthamiana leaves that were either mocked or infiltrated with PVX carrying the empty vector (EV) and PsAvh113. We identified 1769 differentially expressed genes (DEGs) dependent on PsAvh113. Using stricter criteria screening and Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) analysis of DEGs, we found that 38 genes were closely enriched in response to PsAvh113 expression. We selected three genes of N. benthamiana (NbNAC86, NbMyb4, and NbERF114) and found their transcriptional levels significantly upregulated in N. benthamiana infected with PVX carrying PsAvh113. Furthermore, individual silencing of these three genes promoted P. capsici infection, while their overexpression increased resistance to P. capsici in N. benthamiana. Our results show that PsAvh113 interacts with transcription factors NbMyb4 and NbERF114 in vivo. Collectively, these data may help us understand the pathogenic mechanism of effectors and manage PRSR in soybeans.

Varying ratios of M/G in alginate to modulate macrophages polarization and its application for wound healing in diabetic.

Alginate (SA) comprises repeating unis of ß-1, 4 linked ß-D-mannuronic acid (M) and α-L-guloronic acid (G) in varying proportions. The M/G ratio greatly impacts its anti-inflammatory properties in tissue healing wound, as less knowledge reported. This study examined the performances of both SA and SA hydrogel crosslinked with copper ions (SA-Cu) with different M/G ratios are studied. SA with higher M/G ratios stimulated macrophage migration and shifted from M0 to the pro-inflammatory Ml phenotype, while lower M/G ratios shifted from M1 to the pro-repair M2 phenotype. Furthermore, SA-Cu hydrogels with lower M/G ratios exhibited enhanced cross-linking degree, mechanical and rheological properties, as well Cu releasing rate. The reason may be attributed to a relative easy binding between Cu ions and G unit among Cu ions, M unit and G unit. In vitro cell evaluation showed that SA-Cu hydrogel with M/G ratio of 1:1 activated M2 macrophages and up-regulated anti-inflammatory cytokines expression more effectively than those of SA-Cu ratios (2:1) and (1:2). In vivo, SA-Cu hydrogel with M/G ratio of 1:1 expedited diabetic wound healing, accelerating infiltration and phenotype shift of M2 macrophages, and enhancing anti-inflammatory factors, epithelialization and collagen deposition in healing phases. This research highlights the significant role of M/G ratios in SA materials in influencing macrophage behavior and inflammatory responses, which would benefit its application field.

A novel peptide-drug conjugate for glioma-targeted drug delivery.

The existence of the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) greatly limits the application of chemotherapy in glioma. To address this challenge, an optimal drug delivery system must efficiently cross the BBB/BBTB and specifically deliver therapeutic drugs into glioma cells while minimizing systemic toxicity. Here we demonstrated that glucose-regulated protein 78 (GRP78) and dopamine receptor D2 were highly expressed in patient-derived glioma tissues, and dopamine receptors were highly expressed on the BBB. Subsequently, we synthesized a novel "Y"-shaped peptide and compared the effects of different linkers on the receptor affinity and targeting ability of the peptide. A peptide-drug conjugate (pHA-AOHX-VAP-doxorubicin conjugate, pHA-AOHX-VAP-DOX) with a better affinity for glioma cells and higher solubility was derived for glioma treatment. pHA-AOHX-VAP-DOX could cross both BBB and BBTB via dopamine receptor and GRP78 receptor, and finally target glioma cells, significantly prolonging the survival time of nude mice bearing intracranial glioma. Furthermore, pHA-AOHX-VAP-DOX significantly reduced the toxicity of DOX and increased the maximum tolerated dose (MTD). Collectively, this work paves a new avenue for overcoming multiple barriers and effectively delivering chemotherapeutic agents to glioma cells while providing key evidence to identify potential receptors for glioma-targeted drug delivery.

Dual-Frequency Impedance Matching Network Design Using Genetic Algorithm for Power Ultrasound Transducer.

Dual-frequency ultrasounds have demonstrated significant potential in augmenting thermal ablation efficiency for tumor treatment. Ensuring proper impedance matching between the dual-frequency transducer and the power amplifier system is imperative for equipment safety. This paper introduces a novel dual-frequency impedance matching network utilizing L-shaped topology and employing a genetic algorithm to compute component values. Implementation involved an adjustable capacitor and inductor network to achieve dual-frequency matching. Subsequently, the acoustic parameters of the dual-frequency HIFU transducer were evaluated before and after matching, and the effects of ultrasound thermal ablation with and without matching were compared. The proposed dual-frequency impedance matching system effectively reduced the standing wave ratio at the two resonance points while enhancing transmission efficiency. Thermal ablation experiments with matching circuits showed improved temperature rise efficiencies at both frequencies, resulting in an expanded ablation zone. The dual-frequency impedance matching method significantly enhances the transmission efficiency of the dual-frequency ultrasound system at two operational frequencies, thereby ensuring equipment safety. It holds promising prospects for application in dual-frequency ultrasound treatment.

Impact of the extent and location of liver split on future liver remnant hypertrophy after portal vein ligation in a rat model.

BACKGROUND: To investigate the role and mechanism of liver parenchyma transection in accelerating the regeneration of future liver remnants in rats with portal vein ligation (PVL). METHODS: Rats were randomly divided into the PVL group (90% PVL at the caudate lobe, right lobe , left lateral lobe and left median lobe), associating liver partition and portal vein ligation for staged hepatectomy (portal vein ligation with complete liver parenchyma transection [ALPPS]) group (90% PVL with 80 to 90% liver parenchyma transection), PVL + partial liver partition (PLP) group (90% PVL with 30 to 50% liver parenchyma transection), PVL + partition in the ligated lobe (PLL) group (90% PVL with 40 to 60% liver parenchyma transection in the portal vein ligated lobe), PVL + partition in the remnant lobe (PRL) group (90% PVL with 40 to 60% liver parenchyma transection in the remnant lobe), PVL + radiofrequency ablation (RFA) group (90% PVL with splenic ablation) and sham operation (sham) group. The animals were killed at 4 time points of postoperative days 1, 3, 5, and 7. Six rats were killed at each time point, with 24 rats in each group. The weights of the future liver remnant and whole liver were measured. Serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin were analyzed by using an automatic biochemical analyzer. Serum tumor necrosis factor-α, interleukin-6, and hepatocyte growth factor were measured by enzyme-linked immunosorbent assay. The expression of cell proliferating nuclear antigen (Ki67) and phosphorylated histone H3 was detected by immunohistochemistry, and the positive rate was calculated. RESULTS: The ALPPS group displayed the highest FLR weight to body weight ratio compared with that of the other groups (P < .05), and the partial liver split (PVL + PLP) group also displayed higher remnant weight to body weight ratio than the ectopic liver split (PVL + PLL and PVL + PRL) groups (P < .05). During the first 7 days after surgery the cytokine levels of the ALPPS, PVL + PLP, PVL + PLL and PVL + PRL groups were comparable (P > .05). The PVL + PLP, PVL + PLL, PVL + PRL and PVL + RFA groups showed similar necrotic areas in the portal vein ligated lobe (P > .05). A hemodynamic study revealed that a liver split along the demarcation line could further increase the portal pressure of the FLR and both the split site and completeness were associated with portal hemodynamic alternations and liver hypertrophy. Extrahepatic organ injury (eg, spleen ablation) also has a significant impact on portal hemodynamics and liver regeneration. CONCLUSION: Complete liver splitting along the demarcation line induced higher portal vein pressure and more rapid FLR hypertrophy than partial or ectopic liver splitting after PVL. The portal hemodynamic alterations after liver split rather than inflammatory cytokine release may be the major cause of ALPPS-induced rapid liver hypertrophy.

Risk assessment of airborne agricultural pesticide exposure in humans in rural China.

Continuous exposure to airborne pesticides causes their gradual accumulation in the human body, eventually posing a threat to human health. To the best of our knowledge, risk assessment study of pesticide non-occupational exposure to residents in agricultural areas has not been conducted in China. In this study, air samples (gas and dust) were collected from inside and outside residences of seven households and an area near the field in a grain-growing area (wheat and maize rotation) for eight months, and the pesticides present were examined both qualitatively and quantitatively. Using a 95% confidence interval, 9 out of 16 pesticides were detected, namely acetamiprid, acetochlor, atrazine, flucarbazone-sodium, imidacloprid, methyldisulfuron-methyl, nicosulfuron-methyl, pendimethalin, and beta-cyhalothrin, and their safety was subsequently evaluated. The results showed that the inhalation exposure of households to beta-cyhalothrin exceeded the acceptable range in the first residential, and the excess lifetime cancer risk of acetochlor inhalation exposure in six households and area around the field exceeds 1E-6, which highlights the need to strengthen preventive screening for cancer risk.