Comparative Analysis and Future Prospects of Human Epidermal Growth Factor Receptor 2 (HER2) and Trophoblast Cell-Surface Antigen 2 (Trop-2) Targeted Antibody-Drug Conjugates in Breast Cancer Treatment.

Breast cancer remains the most prevalent malignancy among women globally, presenting significant challenges in therapeutic strategies due to tumor heterogeneity, drug resistance, and adverse side effects. Recent advances in targeted therapies, particularly antibody-drug conjugates (ADCs), have shown promise in addressing these challenges by selectively targeting tumor cells while sparing normal tissues. This study provides a comprehensive analysis of two innovative ADCs targeting HER2 and Trop-2, which are critical markers in various breast cancer subtypes. These conjugates combine potent cytotoxic drugs with specific antibodies, leveraging the antigens' differential expression to enhance therapeutic efficacy and reduce systemic toxicity. Our comparative analysis highlights the clinical applications, efficacy, and safety profiles of these ADCs, drawing on data from recent clinical trials. In addition, the paper discusses the potential of these ADCs in treating other types of cancers where HER2 and Trop-2 are expressed, as well as the toxicity risks associated with targeting these antigens in normal cells. Additionally, the paper discusses novel synthetic drugs that show potential in preclinical models, focusing on their mechanisms of action and therapeutic advantages over traditional chemotherapy. The findings underscore the transformative impact of targeted ADCs in breast cancer treatment, noting significant advancements in patient outcomes and management of side effects. However, ongoing issues such as resistance mechanisms and long-term safety remain challenges. The conclusion offers a forward-looking perspective on potential improvements and the future trajectory of ADC research. This study not only elucidates the current landscape of ADCs in breast cancer but also sets the stage for the next generation of oncological therapeutics. This study not only elucidates the current landscape of ADCs in breast cancer but also sets the stage for the next generation of oncological therapeutics, with particular attention to their broader applications and associated risks.

Postoperative PFME versus PFME alone for moderate SUI in pre-menopause women and influencing factors: a comparative effectiveness study.

PURPOSE: To explore the effectiveness of sling surgery followed by pelvic floor muscle exercises (PFME) or PFME alone for moderate stress urinary incontinence (SUI) in women and its influencing factors. METHODS: This is a prospective observational cohort study investigating whether sling surgery or PFME is preferred for pre-menopause women with moderate uncomplicated SUI. Those who received PFME alone or sling surgery were divided to PT or TVT group, respectively. The primary outcome was objective cure at 12 months. The secondary outcomes included Incontinence Impact Questionnaire-Short Form (IIQ-7) scores and PFME adherence. RESULTS: The study sample comprised 130 and 74 patients in the PT and TVT groups, respectively. There was 38.2% of patients adhered to PFME twice weekly or more often, and the compliance varied by education level. At 12 months, the objective cure rate was significantly higher in the TVT versus PT group (75.7% vs 47.7%; adjusted OR = 4.27; 95% CI, 2.05-8.87; P < 0.001). In addition, the mean reduction in IIQ-7 scores was greater in the TVT group (16.2 vs 10.0; adjusted OR = 3.38; 95% CI, 1.93-4.82; P < 0.001). However, among patients with lower education or those without adherence to PFME at 12 months, the TVT was also favorized, and the discrepancy in cure rates was greater between the two groups. CONCLUSION: Sling procedures followed by PFME demonstrate greater efficacy versus physiotherapy alone for moderate female SUI management. Continued adherence to PFME was important, even for patients undergoing sling procedures. Educational factors influenced patient PFME adherence and the advantage conferred by sling procedures.

Study on the metabolic effects of hexavalent chromium [Cr (VI)] on rat astrocytes using un-targeted metabolomics.

Introduction: Hexavalent chromium [Cr (VI)] has been identified as a human carcinogen and environmental pollutant capable of affecting multiple systems in the human body. However, the specific mechanisms by which Cr (VI) affects the human nervous system remain unclear. Objective: Following confirmation of Cr (VI)'s toxic effects on rat astrocytes, this study explores the metabolites and associated metabolic pathways of rat astrocytes under different doses of Cr (VI) exposure. Methods: Cell viability was assessed using CCK8 assays, intracellular reactive oxygen species (ROS) levels were measured using DCFH-DA fluorescent probes, intracellular 8-hydroxydeoxyguanosine (8-OHdG) content was determined by Elisa, mitochondrial membrane potential was observed using JC-1 probes, and key metabolites were identified through untargeted metabolomics analysis. Results: With increasing Cr (VI) doses, significant decreases in cell viability were observed in the 4, 8, and 16 mg/L dose groups (p < 0.05). Elevated levels of ROS and 8-OHdG, increased caspase-3 activity, and significant reductions in mitochondrial membrane potential were observed in the 2 and 4 mg/L dose groups (p < 0.05). Untargeted metabolomics analysis revealed Cr (VI)'s impact on key metabolites such as sphingosine and methionine. Enrichment analysis of KEGG pathways highlighted the critical roles of sphingolipid metabolism and the methionine-cysteine cycle in the effects of Cr (VI) on rat astrocytes. Conclusion: Our study underscores the potential neuro-health risks associated with environmental and occupational exposure to Cr (VI) and provides new perspectives and directions for investigating neurotoxic mechanisms.

Applicability of combined high-frequency and contrast-enhanced ultrasound in finger extensor tendon injuries: three case reports.

BACKGROUND: By combining high-frequency and contrast-enhanced ultrasound (CEUS), the position of the severed end of a finger extensor tendon injury and the injury classification can be determined as part of a comprehensive preoperative evaluation in clinical practice. However, there have been no reports of high-frequency ultrasound combined with CEUS for the preoperative diagnosis of human finger extensor tendon injury. CASES PRESENTATION: One case of complete rupture of the extensor tendon was diagnosed by ultrasound, which was completely consistent with the surgery; one case of incomplete rupture was ultimately confirmed clinically; and one case of distal phalangeal bone base avulsion fracture with tendon contusion and missed diagnosis on the first radiographic examination was confirmed by follow-up radiographic examination. CONCLUSIONS: Different types of finger extensor tendon injuries exhibit distinctive contrast-enhanced ultrasonography findings. Combined high-frequency and contrast-enhanced ultrasound can accurately locate the position of the severed end of the finger extensor tendon injury before surgery while observing the contrast agent filling area to clarify injury classification, providing a reliable imaging basis for clinical practice and ultimately developing personalized diagnosis and treatment plans for patients to ensure minimal trauma and pain, as well as optimal treatment effects.

Identification of hypoxic macrophages in glioblastoma with therapeutic potential for vasculature normalization.

Monocyte-derived tumor-associated macrophages (Mo-TAMs) intensively infiltrate diffuse gliomas with remarkable heterogeneity. Using single-cell transcriptomics, we chart a spatially resolved transcriptional landscape of Mo-TAMs across 51 patients with isocitrate dehydrogenase (IDH)-wild-type glioblastomas or IDH-mutant gliomas. We characterize a Mo-TAM subset that is localized to the peri-necrotic niche and skewed by hypoxic niche cues to acquire a hypoxia response signature. Hypoxia-TAM destabilizes endothelial adherens junctions by activating adrenomedullin paracrine signaling, thereby stimulating a hyperpermeable neovasculature that hampers drug delivery in glioblastoma xenografts. Accordingly, genetic ablation or pharmacological blockade of adrenomedullin produced by Hypoxia-TAM restores vascular integrity, improves intratumoral concentration of the anti-tumor agent dabrafenib, and achieves combinatorial therapeutic benefits. Increased proportion of Hypoxia-TAM or adrenomedullin expression is predictive of tumor vessel hyperpermeability and a worse prognosis of glioblastoma. Our findings highlight Mo-TAM diversity and spatial niche-steered Mo-TAM reprogramming in diffuse gliomas and indicate potential therapeutics targeting Hypoxia-TAM to normalize tumor vasculature.

Learning curve of dynamic navigation-assisted zygomatic implant surgery: An in vitro study.

STATEMENT OF PROBLEM: Dynamic computer-assisted zygomatic implant surgery (dCAZIS) has been reported to provide clinical efficacy with high accuracy and low risk of complications. However, the learning curve before performing dCAZIS effectively is unknown. PURPOSE: The purpose of this in vitro study was to explore the learning curve of dCAZIS in dentists with different levels of experience in implant dentistry and navigation surgery. MATERIAL AND METHODS: Six senior dental students were randomly divided into 3 groups for initial training (FH-CI group: pretraining on freehand conventional implant surgery; FH-ZI group: pretraining on freehand ZI surgery; DN-CI group: pretraining on conventional implant surgery under dynamic navigation). Then, every operator conducted 6 repeated dCAZIS training sessions on edentulous 3-dimensional (3D) printed skull models and was asked to complete a self-report questionnaire after each training session. A total of 36 postoperative cone beam computed tomography (CBCT) scans with 144 ZI osteotomy site preparations were obtained and superimposed over the preoperative design for accuracy measurements. The operation time, 3D deviations, and results of the self-reports were recorded. Comparisons among groups were analyzed with independent-sample Kruskal-Wallis tests (α=.05), and correlations between study outcomes and the number of practices were calculated. RESULTS: Operator experience and increased practice times did not significantly affect the accuracy of dCAZIS (P>.05). However, the operation time varied among groups (P<.001), and significantly shortened with more practice, reaching 11.51 ±1.68 minutes at the fifth attempt in the FH-CI group (P<.001 compared with the first practice), 14.48 ±3.07 minutes at the third attempt in the FH-ZI group (P=.038), and 8.68 ±0.58 minutes at the sixth attempt in the DN-CI group (P<.001). All groups reached their own learning curve plateau stage within 6 practice sessions. As the number of practice sessions increased, the results from the self-report questionnaires gradually improved. CONCLUSIONS: Among dentists with different levels of experience in implant dentistry and navigation surgery, dCAZIS was found to have a learning curve with respect to operation time but not implant accuracy. Experience in ZI surgery had little impact on the learning curve of dCAZIS, but experience in navigation surgery was a key factor.

A combination of laparoscopy and bilateral uterine artery occlusion for the treatment of type II cesarean scar pregnancy: a retrospective analysis.

OBJECTIVE: We investigated the efficacy of a combination of laparoscopy and bilateral uterine artery occlusion (BUAO) for the treatment of type II cesarean scar pregnancy (CSP). METHODS: Patients with type II CSP underwent laparoscopy + bilateral uterine artery embolization (control group) or laparoscopy + BUAO (study group). Data regarding the duration of surgery, intraoperative hemorrhage, postoperative complications, the duration of the hospital stay, and the costs of hospitalization were retrospectively collected. One year later, the time to the return of the ß-human chorionic gonadotropin (ß-hCG) concentration to normal and to the return of menstruation were compared. RESULTS: The duration of surgery, time to the return of menstruation, and incidence of postoperative complications in the study group were significantly less than in the control group, but there was no significant difference in the time for ß-hCG to return to normal or the volume of intraoperative hemorrhage. The duration of hospitalization and costs for the control group were higher than those for the study group. CONCLUSION: Laparoscopy in combination with BUAO is associated with minimal trauma, rapid recovery, a short duration of surgery, low cost of hospitalization, and a low postoperative complication rate. Thus, it represents a useful new surgical treatment for type II CSP.

PGAM1 suppression remodels the tumor microenvironment in triple-negative breast cancer and synergizes with anti-PD-1 immunotherapy.

Triple-negative breast cancer is a high-risk form of breast cancer with a high metastatic potential and lack of effective therapies. Immunotherapy has shown encouraging clinical benefits, and its efficacy in triple-negative breast cancer is affected by immunocyte infiltration in the tumor microenvironment. PGAM1 is a key enzyme involved in cancer metabolism; however, its role in the tumor microenvironment remains unclear. In this study, we aimed to investigate the role of PGAM1 in triple-negative breast cancer and determine the potential of PGAM1 inhibition in combination with anti-PD-1 immunotherapy. Our results showed that PGAM1 is highly expressed in triple-negative breast cancer and is associated with poor prognosis. In vivo experiments demonstrated that PGAM1 inhibition synergizes with anti-PD-1 immunotherapy, significantly remodeling the tumor microenvironment and leading to an increase in antitumor immunocytes, such as CD8+ T cells and M1 macrophages, and a reduction in immunosuppressive cell infiltration, including myeloid-derived suppressor cells, M2 macrophages, and regulatory T cells. Functional and animal experiments showed that this synergistic mechanism inhibited tumor growth in vitro and in vivo. We identified PGAM1 as a novel target that exhibits an antitumor effect via the regulation of immunocyte infiltration. Our results show that PGAM1 can synergize with anti-PD-1 immunotherapy, providing a novel treatment strategy for triple-negative breast cancer.

Analysis of gut microbiota metabolites of platycodin D and activity verification.

As the main saponin component of Platycodon grandiflorum A.DC, Platycodin D has been reported to have an anti-obesity effect. Due to poor oral absorption, the intestinal microflora usually transforms saponins into potential bioactive substances. In this study, we profiled the metabolic changes of platycodin D by incubating it with intestinal microflora extracted from mice feces subjected to either a standard control diet or a high-fat diet. A UPLC-LTQ-Orbitrap-MS method was used for rapid analysis of the metabolic profile of platycodin D. A total of 10 compounds were identified 9 of which were assessed to be metabolized by intestinal microflora. Dehydroxylation and deglycosylation were the major metabolic process of platycodin D. The metabolic profile of platycodin D biotransformed by intestinal microflora was elucidated based on the metabolite information. Platycodin D and its metabolites had anti-inflammatory effects in LPS-stimulated RAW 264.7 cells. Only platycodin D could alleviate lipid accumulation in FFA-treated HepG2 cells.

Small G-Protein Rheb Gates Mammalian Target of Rapamycin Signaling to Regulate Morphine Tolerance in Mice.

BACKGROUND: Analgesic tolerance due to long-term use of morphine remains a challenge for pain management. Morphine acts on µ-opioid receptors and downstream of the phosphatidylinositol 3-kinase signaling pathway to activate the mammalian target of rapamycin (mTOR) pathway. Rheb is an important regulator of growth and cell-cycle progression in the central nervous system owing to its critical role in the activation of mTOR. The hypothesis was that signaling via the GTP-binding protein Rheb in the dorsal horn of the spinal cord is involved in morphine-induced tolerance. METHODS: Male and female wild-type C57BL/6J mice or transgenic mice (6 to 8 weeks old) were injected intrathecally with saline or morphine twice daily at 12-h intervals for 5 consecutive days to establish a tolerance model. Analgesia was assessed 60 min later using the tail-flick assay. After 5 days, the spine was harvested for Western blot or immunofluorescence analysis. RESULTS: Chronic morphine administration resulted in the upregulation of spinal Rheb by 4.27 ± 0.195-fold (P = 0.0036, n = 6), in turn activating mTOR by targeting rapamycin complex 1 (mTORC1). Genetic overexpression of Rheb impaired morphine analgesia, resulting in a tail-flick latency of 4.65 ± 1.10 s (P < 0.0001, n = 7) in Rheb knock-in mice compared to 10 s in control mice (10 ± 0 s). Additionally, Rheb overexpression in spinal excitatory neurons led to mTORC1 signaling overactivation. Genetic knockout of Rheb or inhibition of mTORC1 signaling by rapamycin potentiated morphine-induced tolerance (maximum possible effect, 52.60 ± 9.56% in the morphine + rapamycin group vs. 16.60 ± 8.54% in the morphine group; P < 0.0001). Moreover, activation of endogenous adenosine 5'-monophosphate-activated protein kinase inhibited Rheb upregulation and retarded the development of morphine-dependent tolerance (maximum possible effect, 39.51 ± 7.40% in morphine + metformin group vs. 15.58 ± 5.79% in morphine group; P < 0.0001). CONCLUSIONS: This study suggests spinal Rheb as a key molecular factor for regulating mammalian target of rapamycin signaling.

Mechanisms of shoulder dislocation explained in the "hand as foot teaching philosophy".

OBJECTIVE: To continuously absorb new teaching concepts and try new teaching methods in the process of clinical practice teaching for medical students to improve the teaching effect. METHODS: In the process of clinical practice teaching of orthopedic, the teaching concept of "hand and foot" was adopted. RESULTS: In the process of clinical practice teaching for medical students, the "hand as foot teaching philosophy" was used to explain the abstract anatomical structures, which greatly stimulated students' interest in classroom learning and achieved good teaching effects. CONCLUSION: The "hand as foot teaching philosophy" is a new teaching concept, which is worth exploring and applying in clinical practice, so as to continuously optimize and improve the theoretical system and better serve for teaching.

Clinical efficacy of computer-assisted zygomatic implant surgery: A systematic scoping review.

STATEMENT OF PROBLEM: Digital technology can improve the success of zygomatic implant (ZI) surgery. However, the reliability and efficacy of computer-assisted zygomatic implant surgery (CAZIS) need further analysis. PURPOSE: The purpose of this scoping review was to provide an overview of the placement accuracy, implant survival, and complications of CAZIS. MATERIAL AND METHODS: A systematic search of English and Mandarin Chinese publications up to May 2023 was conducted in PubMed, Web of Science, Embase, and Wanfang database. The nonpeer-reviewed literature was searched in the trial register (clinicaltrials.gov). Clinical studies and cadaver studies on CAZIS were included. After data extraction and collection, the findings were critically reviewed, analyzed, interpreted, and discussed. RESULTS: Forty-one studies met the inclusion criteria. After excluding publications with duplicate data, retaining the most recent, 28 articles were included in this scoping review. Of these, 18 were on static computer-assisted zygomatic implant surgery (sCAZIS), 8 on dynamic computer-assisted zygomatic implant surgery (dCAZIS), and 2 on robot-assisted zygomatic implant surgery (rAZIS). Excluding the outliers, the mean deviations of ZIs in the sCAZIS group (with 8 articles reporting implant placement accuracy, 183 ZIs involved) were: 1.15 ±1.37 mm (coronal deviation), 2.29 ±1.95 mm (apical deviation), and 3.32 ±3.36 degrees (angular deviation). The mean deviations of dCAZIS (3 articles, 251 ZIs) were: 1.60 ±0.74 mm (coronal), 2.27 ±1.05 mm (apical), and 2.89 ±1.69 degrees (angular). The mean deviations of rAZIS (2 articles, 5 ZIs) were: 0.82 ±0.21 mm (coronal), 1.25 ±0.52 mm (apical), and 1.46 ±0.35 degrees (angular). Among the CAZIS reported in the literature, the implant survival rate was high (96.3% for sCAZIS, 98.2% for dCAZIS, and 100% for rAZIS, specified in 14 of 21 clinical studies). The incidence of complications was low, but, because of the few relevant studies (4/21 specified), valid conclusions regarding complications could not be drawn. CONCLUSIONS: CAZIS has demonstrated clinical efficacy with high implant survival rates and placement accuracy. Of the 3 guided approaches, rAZIS showed the smallest 3-dimensional deviation.

Deer antlers: the fastest growing tissue with least cancer occurrence.

Deer antlers are a bony organ solely able to acquired distinct unique attributes during evolution and all these attributes are against thus far known natural rules. One of them is as the fastest animal growing tissue (2 cm/day), they are remarkably cancer-free, despite high cell division rate. Although tumor-like nodules on the long-lived castrate antlers in some deer species do occur, but they are truly benign in nature. In this review, we tried to find the answer to this seemingly contradictory phenomenon based on the currently available information and give insights into possible clinic application. The antler growth center is located in its tip; the most intensive dividing cells are resident in the inner layer of reserve mesenchyme (RM), and these cells are more adopted to osteosarcoma rather than to normal bone tissues in gene expression profiles but acquire their energy mainly through aerobic oxidative phosphorylation pathway. To counteract propensity of neoplastic transformation, antlers evolved highly efficient apoptosis exactly in the RM, unparalleled by any known tissues; and annual wholesale cast to jettison the corps. Besides, some strong cancer suppressive genes including p53 cofactor genes and p53 regulator genes are highly positively selected by deer, which would have certainly contributed to curb tumorigenesis. Thus far, antler extracts and RM cells/exosomes have been tried on different cancer models either in vitro or in vivo, and all achieved positive results. These positive experimental results together with the anecdotal folklore that regular consumption of velvet antler is living with cancer-free would encourage us to test antlers in clinic settings.

Postoperative ratio of C-reactive protein to albumin is an independent prognostic factor for gastric cancer.

OBJECTIVE: The role of postoperative of the ratio of c-reactive protein to albumin (CRP/Alb ratio) in the prognosis of gastric cancer is rarely evaluated. Our purpose was to investigate the correlation of the postoperative CRP/Alb ratio and long-term prognosis of gastric cancer. METHODS: We enrolled 430 patients who suffered from radical gastrectomy. The commonly used inflammatory indices, clinical-pathological characteristics and oncologic outcomes were recorded. The median was used to the cut-off value for preoperative and postoperative CRP/Alb ratio, respectively. Kaplan-Meier analysis and Cox proportional hazards regression model were performed to determine its prognostic significance. RESULTS: In univariate analysis, there were significant differences were observed in overall survival (OS) according to perioperative CRP/Alb ratio, c-reactive protein (CRP), serum albumin (Alb), respectively. According to the multivariate analysis, higher postoperative CRP/Alb ratio (HR 2.03, 95% CI 1.55-2.66, P < 0.001), lower postoperative albumin (Alb), higher preoperative c-reactive protein (CRP) and higher postoperative CRP were indicated a shorter overall survival. CONCLUSION: Postoperative inflammatory factors in patients with gastric cancer should be pay attention, especially postoperative CRP/Alb ratio may be an independent predictor of long-term prognosis of gastric cancer.

A deep learning-based automatic segmentation of zygomatic bones from cone-beam computed tomography images: A proof of concept.

OBJECTIVES: To investigate the efficiency and accuracy of a deep learning-based automatic segmentation method for zygomatic bones from cone-beam computed tomography (CBCT) images. METHODS: One hundred thirty CBCT scans were included and randomly divided into three subsets (training, validation, and test) in a 6:2:2 ratio. A deep learning-based model was developed, and it included a classification network and a segmentation network, where an edge supervision module was added to increase the attention of the edges of zygomatic bones. Attention maps were generated by the Grad-CAM and Guided Grad-CAM algorithms to improve the interpretability of the model. The performance of the model was then compared with that of four dentists on 10 CBCT scans from the test dataset. A p value <0.05 was considered statistically significant. RESULTS: The accuracy of the classification network was 99.64%. The Dice coefficient (Dice) of the deep learning-based model for the test dataset was 92.34 ± 2.04%, the average surface distance (ASD) was 0.1 ± 0.15 mm, and the 95% Hausdorff distance (HD) was 0.98 ± 0.42 mm. The model required 17.03 s on average to segment zygomatic bones, whereas this task took 49.3 min for dentists to complete. The Dice score of the model for the 10 CBCT scans was 93.2 ± 1.3%, while that of the dentists was 90.37 ± 3.32%. CONCLUSIONS: The proposed deep learning-based model could segment zygomatic bones with high accuracy and efficiency compared with those of dentists. CLINICAL SIGNIFICANCE: The proposed automatic segmentation model for zygomatic bone could generate an accurate 3D model for the preoperative digital planning of zygoma reconstruction, orbital surgery, zygomatic implant surgery, and orthodontics.

Priming effects of nZVI on carbon sequestration and iron uptake are positively mediated by AM fungus in semiarid agricultural soils.

We investigated the priming effect of nanoscale zero-valent iron (nZVI) on carbon sink and iron uptake, and the possible mediation by AMF (arbuscular mycorrhizal fungi, Funneliformis mosseae) in semiarid agricultural soils. Maize seed dressings comprised of three nZVI concentrations of 0, 1, 2 g·kg-1 and was tested with and without AMF inoculation under high and low soil moistures, respectively. The ICP-OES observations indicated that both low dose of nZVI (1 g·kg-1) and high dose of nZVI (2 g·kg-1) significantly increased the iron concentrations in roots (L: 54.5-109.8 %; H: 119.1-245.4 %) and shoots (L: 40.8-78.9 %; H: 81.1-99.4 %). Importantly, the absorption and translocation rate of iron were substantially improved by AMF inoculation under the low-dose nZVI. Yet, the excess nanoparticles as a stress were efficiently relieved by rhizosphere hyphae, and the iron concentration in leaves and stems can maintain as high as about 300 mg·kg-1 while the iron translocation efficiency was reduced. Moreover, next-generation sequencing confirmed that appropriate amount of nZVI clearly improved the rhizosphere colonization of Funneliformis mosseae (p < 0.001) and the development of soil fungal community. Soil observations further showed that the hyphae development and GRSP (glomalin-related soil protein) secretion were significantly promoted (p < 0.05), with the increased R0.25 (< 0.25 mm) by 35.97-41.16 %. As a return, AMF and host plant turned to input more organic matter into soils for microbial growth and Fe uptake, and such interactions became more pronounced under drought stress. In contrast, high dose of nZVI (2 g·kg-1) tended to agglomerate on the surface of hyphae and spores, causing severe deformation and inactivation of AMF symbionts. Therefore, the priming effects of nZVI on carbon sequestration and Fe uptake in agricultural soils were positively mediated by AMF via the feedback loop of the plant-soil-microbe system for enhanced adaptation to global climate change.

Microureteroscopy in the treatment of upper urinary tract stones in pediatric patients younger than 3 years of age.

The aim of this study is to evaluate the usefulness of microureteroscopy (m-URS) in the treatment of renal and ureteral stones in children younger than 3 years of age. A retrospective analysis of pediatric patients aged < 3 years with upper urinary tract calculi who underwent lithotripsy was performed. The children were divided into the m-URS group (4.85 F, n = 41) and the ureteroscopy (URS) group (4.5/6.5 F, n = 42) according to the type of ureteroscope used. The mean age of the patients was 23.5 ± 10.7 months in the m-URS group and 20.6 ± 7.1 months in the URS group (P = 0.212). The success rate of one-stage surgery was 80.5% (33/41) for m-URS and 38.1% (16/42) for URS (P < 0.001). The success rates of m-URS were 60.0%, 69.2%, and 91.3% for stones located in the renal pelvis/calix, upper ureter, and mid-lower ureter, respectively. Eight children in the m-URS group and 26 children in the URS group underwent the second-stage ureteroscopic surgery. The mean operation time was 50 (30-60) min in the m-URS group and 40 (34-60) min in the URS group (P = 0.287). The complication rates were 4.9% and 7.1% in the m-URS and URS groups, respectively (P = 1.000). The stone-free rate at 1 month after lithotripsy was 87.8% in the m-URS group and 83.3% in the URS group (P = 0.563). The mean anesthesia session was 2.1 in the m-URS group and 2.5 in the URS group (P = 0.002). M-URS can effectively reduce the number of anesthesia sessions and is considered an alternative treatment for upper urinary tract calculi in selected pediatric patients younger than 3 years of age.

Mitigation mechanism of zinc oxide nanoparticles on cadmium toxicity in tomato.

Cadmium (Cd) pollution seriously reduces the yield and quality of vegetables. Reducing Cd accumulation in vegetables is of great significance for improving food safety and sustainable agricultural development. Here, using tomato as the material, we analyzed the effect of foliar spraying with zinc oxide nanoparticles (ZnO NPs) on Cd accumulation and tolerance in tomato seedlings. Foliar spraying with ZnO NPs improved Cd tolerance by increasing photosynthesis efficiency and antioxidative capacity, while it reduced Cd accumulation by 40.2% in roots and 34.5% in leaves but increased Zn content by 33.9% in roots and 78.6% in leaves. Foliar spraying with ZnO NPs also increased the contents of copper (Cu) and manganese (Mn) in the leaves of Cd-treated tomato seedlings. Subsequent metabonomic analysis showed that ZnO NPs exposure alleviated the fluctuation of metabolic profiling in response to Cd toxicity, and it had a more prominent effect in leaves than in roots. Correlation analysis revealed that several differentially accumulated metabolites were positively or negatively correlated with the growth parameters and physiol-biochemical indexes. We also found that flavonoids and alkaloid metabolites may play an important role in ZnO NP-alleviated Cd toxicity in tomato seedlings. Taken together, the results of this study indicated that foliar spraying with ZnO NPs effectively reduced Cd accumulation in tomato seedlings; moreover, it also reduced oxidative damage, improved the absorption of trace elements, and reduced the metabolic fluctuation caused by Cd toxicity, thus alleviating Cd-induced growth inhibition in tomato seedlings. This study will enable us to better understand how ZnO NPs regulate plant growth and development and provide new insights into the use of ZnO NPs for improving growth and reducing Cd accumulation in vegetables.

Ginseng-based carbon dots inhibit the growth of squamous cancer cells by increasing ferroptosis.

Background: Recent studies indicated that Ginseng potentiate cancer treatments. Ginseng-based carbon dots (GCDs) might possess properties to kill cancer cells and inhibit malignant tumor development and invasion. This study aimed to prepare GCDs, examine their effects on cancer cell growth and invasion, and explore the mechanisms involved. Methods: GCDs were synthesized, purified, and characterized. Cells were cultured with GCDs and were tested for growth, invasiveness, and wound healing. RNA was extracted for transcriptomics analysis. Protein expression was evaluated using western blot and immunohistochemistry. Mice were injected with cancer cells and treated with PBS or GCDs. Tumor volume was evaluated. Results: GCDs were successfully synthesized and purified. The solution was yellow under sunlight and fluorescent blue under ultraviolet light. Electron microscopy showed GCDs with a uniform shape without apparent aggregation and an average diameter of about 4 nm. GCDs inhibited Cal-27, SCC-25, and SCC-7 cancer cell growth at concentrations of >250-300 µg/mL, while GCDs inhibited the non-cancerous HaCaT cells at concentrations >400 µg/mL. Immunofluorescence showed that GCDs could enter the cells. Transcriptomics revealed 552 downregulated mRNAs and 338 upregulated ones, including mRNAs involved in the oxidative phosphorylation and ferroptosis pathways. GCDs induced the ferroptosis of cancer cells, as shown by decreased GPX-4 and increased COX-2. GCDs decreased cell invasion and migration. In vivo, GCDs decreased tumor growth without apparent organ toxicity and promoted CD4+ T cell infiltration in the tumor. Conclusion: GCDs appear to possess anticancer properties by increasing ferroptosis, resulting in cancer cell growth inhibition in vitro and in vivo.

Triptolide protects human retinal pigment epithelial ARPE-19 cells against high glucose-induced cell injury by regulation of miR-29b/PTEN.

Oxidative stress and inflammation are necessary pathogenic factors contributing to the aetiology of diabetic retinopathy (DR). Triptolide (TPL) is derived from the traditional Chinese herb lei gong teng with anti-inflammatory, immunosuppressive and antitumor activities. This article was developed to examine the effect of TPL on DR. ARPE-19 cells were pre-treated with TPL and then stimulated by high glucose (HG). We found that TPL treatment enhanced cell viability, decreased apoptosis and ROS production in HG-treated RPE cells. MiR-29b was low-expressed in HG-treated cells, but TPL raised its expression. In addition, the protective activity of TPL towards ARPE-19 cells was attenuated when miR-29b was reduced. By utilising bioinformatics evaluation, PTEN was predicted as a downstream target of miR-29b. Also, TPL obstructed PI3K/AKT signalling pathways in HG-treated ARPE-19 Cells. Taken together, TPL secured ARPE-19 cells from HG-induced oxidative damage via regulating miR-29b/PTEN axis.