Spraying performance and deposition characteristics of an improved air-assisted nozzle with induction charging.

Electrostatic spraying technology can improve the efficiency of pesticide deposition on the surface of leaves and reduce the environmental pollution caused by pesticide drift, which has an important prospect in agricultural pesticide application. To improve the deposition and penetration of droplets in the crop canopy, we designed and optimized an air-assisted electrostatic nozzle and conducted the spraying performance experiment. Parameters, such as charge-to-mass ratio (CMR) and particle size, were tested and analyzed to obtain the suitable operating parameters of nozzle. The results proved that the improved air-assisted electrostatic nozzle has good atomization and chargeability. There is a good charging effect with a charging voltage of 3,000-5,000 V, the CMR increased 127.8% from 0.86 to 1.97 mC/kg as the charge voltage increases from 1,000 to 4,000 V, at an air pressure of 1.0 bar and liquid flow rate of 200 ml/min. Furthermore, we designed a multi-factor orthogonal experiment, which was conducted using a four-factor, three-level design to investigate the effects of operational parameters and canopy characteristics on droplet deposition and penetration. Analysis of variance (ANOVA) and F-test were performed on the experiment results. The results showed that the factor effect on droplet penetration, in descending order, was as follows: spray distance, leaf area index, air pressure, and air pressure × spray distance. The factor effect on abaxial leaf deposition, in descending order, was as follows: air pressure, spray distance, air pressure × charge voltage, spray distance × charge voltage, and charge voltage. For optimal droplet penetration and abaxial leaf deposition, option A 3 B 1 D 2 (air pressure 1.5 bar, spray distance 0.2 m, charge voltage 2,500 V) is recommend. The spray nozzle atomization performance and deposition regulation were studied by experimental methods to determine the optimal values of operating parameters to provide a reference for electrostatic spray system development.

Assembly and comparative analysis of the initial complete mitochondrial genome of Primulina hunanensis (Gesneriaceae): a cave-dwelling endangered plant.

BACKGROUND: Primulina hunanensis, a troglobitic plant within the Primulina genus of Gesneriaceae family, exhibits robust resilience to arid conditions and holds great horticultural potential as an ornamental plant. The work of chloroplast genome (cpDNA) has been recently accomplished, however, the mitochondrial genome (mtDNA) that is crucial for plant evolution has not been reported. RESULTS: In this study, we sequenced and assembled the P. hunanensis complete mtDNA, and elucidated its evolutionary and phylogenetic relationships. The assembled mtDNA spans 575,242 bp with 43.54% GC content, encompassing 60 genes, including 37 protein-coding genes (PCGs), 20 tRNA genes, and 3 rRNA genes. Notably, high number of repetitive sequences in the mtDNA and substantial sequence translocation from chloroplasts to mitochondria were observed. To determine the evolutionary and taxonomic positioning of P. hunanensis, a phylogenetic tree was constructed using mitochondrial PCGs from P. hunanensis and 32 other taxa. Furthermore, an exploration of PCGs relative synonymous codon usage, identification of RNA editing events, and an investigation of collinearity with closely related species were conducted. CONCLUSIONS: This study reports the initial assembly and annotation of P. hunanensis mtDNA, contributing to the limited mtDNA repository for Gesneriaceae plants and advancing our understanding of their evolution for improved utilization and conservation.

Role of ablation therapy in conjunction with surgical resection for neuroendocrine tumors involving the liver.

BACKGROUND: Resection of hepatic metastasis from neuroendocrine tumors (NETs) improves quality of life and prolongs 5-year survival. Ablation can be utilized with surgery to achieve complete resection. Although several studies report long-term outcomes for patients undergoing ablation, none have explored perioperative effects of ablation in patients with metastatic NETs. AIM: To determine if intra-operative ablation during hepatectomy increases risk of adverse outcomes such as surgical site infections (SSIs), bleeding, and bile leak. METHODS: A retrospective analysis of the hepatectomy National Surgical Quality Improvement Program database from 2015-2019 was performed to determine the odds of SSIs, bile leaks, or bleeding in patients undergoing intraoperative ablation when compared to hepatectomy alone. RESULTS: Of the 966 patients included in the study, 298 (30.9%) underwent ablation during hepatectomy. There were 78 (11.7%) patients with SSIs in the hepatectomy alone group and 39 (13.1%) patients with a SSIs in the hepatectomy with ablation group. Bile leak occurred in 41 (6.2%) and 14 (4.8%) patients in the two groups, respectively; bleeding occurred in 117 (17.5%) and 33 (11.1%), respectively. After controlling for confounding variables, ablation did not increase risk of SSI (P = 0.63), bile leak (P = 0.34) or bleeding (P = 0.07) when compared to patients undergoing resection alone on multivariate analysis. CONCLUSION: Intraoperative ablation with hepatic resection for NETs is safe in the perioperative period without significant increased risk of infection, bleeding, or bile leak. Surgeons should utilize this modality when appropriate to achieve optimal disease control and outcomes.

Effects of isorhamnetin on liver injury in heat stroke-affected rats under dry-heat environments via oxidative stress and inflammatory response.

Isorhamnetin is a natural flavonoid compound, rich in brass, alkaloids, and sterols with a high medicinal value. This study investigated the effects of isorhamnetin on liver injury and oxidative and inflammatory responses in heat-stroke-affected rats in a dry-heat environment. Fifty Sprague Dawley rats were randomly divided into five groups: normal temperature control (NC, saline), dry-heat control (DHC, saline), low-dose isorhamnetin-pretreated (L-AS, 25 mg/Kg), medium-dose isorhamnetin-pretreated (M-AS, 50 mg/Kg), and high-dose isorhamnetin-pretreated (H-AS, 100 mg/Kg) group. Saline was administered to the NC and DHC groups and corresponding concentrations of isorhamnetin were administered to the remaining three groups for 1 week. Blood and liver tissue were analyzed for oxidative stress and inflammation. The liver histopathological injury score, serum liver enzyme (alanine transaminase, aspartate transaminase, and lactate dehydrogenase), liver oxidative stress index (superoxide dismutase [SOD], catalase [CAT], and malondialdehyde), and inflammation index (tumor necrosis factor α [TNF-α], interleukin [IL]-1ß, IL-6, and lipopolysaccharides) were significantly higher in the DHC group than in the NC group (P < 0.05). These index values in the L-AS, M-AS, and H-AS groups were significantly lower than those in the DHC group (P < 0.05). The index values decreased significantly with an increase in the concentration of isorhamnetin (P < 0.05), while the index values of CAT and SOD showed the opposite tendency (P < 0.05). The expression of liver tissue nuclear factor kappa B (NF-κB), caspase-3, and heat shock protein (HSP-70) was higher in the DHC group than in the NC group (P < 0.05). Comparison between the isorhamnetin and DHC groups revealed that the expression of NF-кB and caspase-3 was decreased, while that of HSP-70 continued to increase (P < 0.05). The difference was significant for HSP-70 among all the isorhamnetin groups (P < 0.05); however, the NF-кB and caspase-3 values in the L-AS and H-AS groups did not differ. In summary, isorhamnetin has protective effects against liver injury in heat-stroke-affected rats. This protective effect may be related to its activities concerning antioxidative stress, anti-inflammatory response, inhibition of NF-кB and caspase-3 expression, and enhancement of HSP-70 expression.

Flying Target Detection Technology Based on GNSS Multipath Signals.

In this study, a passive radar system that detects flying targets is developed in order to solve the problems associated with traditional flying target detection systems (i.e., their large size, high power consumption, complex systems, and poor battlefield survivability). On the basis of target detection, the system uses the multipath signal (which is usually eliminated as an error term in navigation and positioning), enhances it by supporting information, and utilizes the multi-source characteristics of ordinary omnidirectional global navigation satellite system (GNSS) signals. The results of a validation experiment showed that the system is able to locate a passenger airplane and obtain its flight trajectory using only one GNSS receiving antenna. The system is characterized by its light weight (less than 5 kg), low power consumption, simple system, good portability, low cost, and 24/7 and all-weather work. It can be installed in large quantities and has good prospects for development.

MKRN1 regulates the expression profiles and transcription factor activity in HeLa cells inhibition suppresses cervical cancer cell progression.

Cervical cancer is one of the most common gynecologic malignancies worldwide, necessitating the identification of novel biomarkers and therapeutic targets. This study aimed to investigate the significance of MKRN1 in cervical cancer and explore its potential as a diagnostic marker and therapeutic target. The results indicated that MKRN1 expression was up-regulated in cervical cancer tissues and correlated with advanced tumor stage, higher grade, and poor patient survival. Functional studies demonstrated that targeting MKRN1 effectively inhibited cell proliferation, migration, and invasion, highlighting its critical role in tumor progression and metastasis. Moreover, the knockdown of MKRN1 resulted in altered expression patterns of six transcription factor-encoding genes, revealing its involvement in gene regulation. Co-expression network analysis unveiled complex regulatory mechanisms underlying the effects of MKRN1 knockdown on gene expression. Furthermore, the results suggested that MKRN1 might serve as a diagnostic marker for personalized treatment strategies and a therapeutic target to inhibit tumor growth, metastasis, and overcome drug resistance. The development of MKRN1-targeted interventions might hold promise for advancing personalized medicine approaches in cervical cancer treatment. Further research is warranted to validate these findings, elucidate underlying mechanisms, and translate these insights into improved management and outcomes for cervical cancer patients.

Sirt5-mediated lysine desuccinylation regulates oxidative stress adaptation in Magnaporthe oryzae during host intracellular infection.

Plant pathogenic fungi elaborate numerous detoxification strategies to suppress host reactive oxygen species (ROS), but their coordination is not well-understood. Here, we show that Sirt5-mediated protein desuccinylation in Magnaporthe oryzae is central to host ROS detoxification. SIRT5 encodes a desuccinylase important for virulence via adaptation to host oxidative stress. Quantitative proteomics analysis identified a large number of succinylated proteins targeted by Sirt5, most of which were mitochondrial proteins involved in oxidative phosphorylation, TCA cycle, and fatty acid oxidation. Deletion of SIRT5 resulted in hypersuccinylation of detoxification-related enzymes, and significant reduction in NADPH : NADP+ and GSH : GSSG ratios, disrupting redox balance and impeding invasive growth. Sirt5 desuccinylated thioredoxin Trx2 and glutathione peroxidase Hyr1 to activate their enzyme activity, likely by affecting proper folding. Altogether, this work demonstrates the importance of Sirt5-mediated desuccinylation in controlling fungal process required for detoxifying host ROS during M. oryzae infection.

Structure, Synthesis, and Bioassays of Sex Pheromone for Pyrausta machaeralis (Lepidoptera: Crambidae).

The leaf skeletonizer, Pyrausta machaeralis (Lepidoptera: Crambidae), is a serious insect pest of teak (Tectona grandis) in China. The application of insect pheromones is widely applied as an environmentally friendly technology for integrated pest management (IPM). In the present study, crude extracts of sex pheromone glands of calling P. machaeralis females were collected and then analyzed using gas chromatography/electroantennographic detection (GC/EAD) and gas chromatography-mass spectrometry (GC-MS). The combination of infrared spectroscopy (IR) and nuclear magnetic resonance (NMR) spectrometry was used for structure identification. Afterward, their electrophysiological and behavioral activity was evaluated in the laboratory and field. Herein, we eventually determined two active components, E-11-tetradecenyl acetate (E11-14:Ac) and Z-11-tetradecenyl acetate (Z11-14:Ac), at a ratio of 96:4, as the sex pheromone of P. machaeralis. The identification of sex pheromones would facilitate the development of efficient strategies for monitoring and controlling the field populations of P. machaeralis.

Post-operative morbidity after neoadjuvant chemotherapy and resection for gallbladder cancer: A national surgical quality improvement program analysis.

BACKGROUND: Gallbladder cancer is the most common malignancy of the biliary tract. Neoadjuvant chemotherapy (NACT) has improved overall survival by enabling R0 resection. Currently, there is no consensus of guidelines for neoadjuvant therapy in gallbladder cancer. As investigations continue to analyze the regimen and benefit of NACT for ongoing care of gallbladder cancer patients, we examined American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database to determine if there was higher morbidity among the neoadjuvant group within the 30-day post-operative period. We hypothesized patients who underwent NACT were more likely to have higher post-operative morbidity. AIM: To investigate the 30-day post-operative morbidity outcomes between patients who received NACT and underwent surgery and patients who only had surgery. METHODS: A retrospective analysis of the targeted hepatectomy NSQIP data between 2015 and 2019 was performed to determine if NACT in gallbladder cancer increased the risk for post-operative morbidity (bile leak, infection rate, rate of converting to open surgery, etc.) compared to the group who only had surgery. To calculate the odds ratio for the primary and secondary outcomes, a crude logistic regression was performed. RESULTS: Of the 452 patients, 52 patients received NACT prior to surgery. There were no statistically significant differences in the odds of morbidity between the two groups, including bile leak [odds ratio (OR), 0.69; 95% confidence interval (95%CI): 0.16-2.10; P = 0.55], superficial wound infection (OR, 0.58; 95%CI: 0.03-3.02; P = 0.61), and organ space wound infection (OR, 0.63; 95%CI: 0.18-1.63; P = 0.61). CONCLUSION: There was no significant difference in the risk of 30-day post-operative morbidity between the NACT and surgery group and the surgery only group.

miR-30c affects the pathogenesis of ulcerative colitis by regulating target gene VIP.

MicroRNAs play a crucial role in regulating the epithelial barrier and immune response, which are implicated in the pathogenesis of ulcerative colitis (UC). This study aimed to investigate the role and molecular mechanism of miR-30c in the pathogenesis of UC using a dextran sulfate sodium salt (DSS)-induced colitis model, which is similar to ulcerative colitis. Wild-type (WT) and miR-30c knockout (KO) mice were assigned to either control or DSS-treated groups to evaluate the influence of aberrant miR-30c expression on UC pathogenesis. The disease activity index, inflammatory factors, and the extent of pathological and histological damage in colon tissues were analyzed. The effect of miR-30c on vasoactive intestinal peptide (VIP) gene expression was validated through luciferase reporter assay, qRT-PCR, Western blotting, and immunohistochemistry. The results showed that miR-30c KO mice with DSS-induced colitis model showed more severe phenotypes: significantly higher disease activity indices, significant body weight loss, reduced length of the colon of mice, increased number of aberrant crypt structures, reduced mucus secretion, and significant differences in inflammatory factors. These findings suggested that the absence of miR-30c might promote DSS-induced colitis, and the targe-regulatory effect of miR-30c on VIP might play an important role in the development of colitis.

A novel role for the ROS-ATM-Chk2 axis mediated metabolic and cell cycle reprogramming in the M1 macrophage polarization.

Reactive oxygen species (ROS) play a pivotal role in macrophage-mediated acute inflammation. However, the precise molecular mechanism by which ROS regulate macrophage polarization remains unclear. Here, we show that ROS function as signaling molecules that regulate M1 macrophage polarization through ataxia-telangiectasia mutated (ATM) and cell cycle checkpoint kinase 2 (Chk2), vital effector kinases in the DNA damage response (DDR) signaling pathway. We further demonstrate that Chk2 phosphorylates PKM2 at the T95 and T195 sites, promoting glycolysis and facilitating macrophage M1 polarization. In addition, Chk2 activation increases the Chk2-dependent expression of p21, inducing cell cycle arrest for subsequent macrophage M1 polarization. Finally, Chk2-deficient mice infected with lipopolysaccharides (LPS) display a significant decrease in lung inflammation and M1 macrophage counts. Taken together, these results suggest that inhibiting the ROS-Chk2 axis can prevent the excessive inflammatory activation of macrophages, and this pathway can be targeted to develop a novel therapy for inflammation-associated diseases and expand our understanding of the pathophysiological functions of DDR in innate immunity.

Heat-triggered shape recovery, EMI shielding and flame retardant: A novel cellulose/M(OH)(OCH3)@dopamine@Ag (M=Co, Ni) nanopaper for early fire alarm.

Fire alarm systems are essential for protecting lives and properties from fire hazards. However, most of the existing fire alarm nanopapers rely on the resistance reduction after heating, which requires direct contact with the flame. In this study, we present a novel fire alarm nanopaper (CMPA) based on heat-triggered shape recovery. The CMPA is composed of hydroxypropyl methyl cellulose (HPMC) as the matrix and 2D nanomaterials M(OH)(OCH3) as fillers. When the temperature of CMPA exceeded the glass transition, the thrice-folded CMPA-1.0 flattened in 30s and connected to the alarm circuit based on its conductive surface. According to the results, the CMPA-1.0 with a thickness of about 0.2 mm had an efficient electromagnetic shielding of 42.1 dB. Moreover, the CMPA-1.0 self-extinguished rapidly after being ignited with its original shape preserved. The peak heat release rate of CMPA-1.0 was 108.9 W/g, which was 61.9 % lower than that of HPMC. Furthermore, the thermal conductivity of CMPA-1.0 reached to 0.317 W m-1 K-1, which was 40.8 % higher than that of HPMC, reducing the heat accumulation effectively. This work shows that CMPA is an ideal material for sensitive and safe early fire alarm, and the strategy based on heat-triggered shape recovery is promising in fire alarm application.

Nanocurcumin attenuates pyroptosis and inflammation through inhibiting NF-κB/GSDMD signal in high altitude-associated acute liver injury.

Exposure to a hypobaric hypoxic environment at high altitudes can lead to liver injury, and mounting evidence indicates that pyroptosis and inflammation play important roles in liver injury. Curcumin (Cur) can inhibit pyroptosis and inflammation. Therefore, our purpose here was to clarify the mechanism underlying the protective effect of nanocurcumin (Ncur) and Cur in a rat model of high altitude-associated acute liver injury. Eighty healthy rats were selected and exposed to different altitudes (6000 or 7000 m) for 0, 24, 48, or 72 h. Fifty normal healthy rats were divided into normal control, high-altitude control, salidroside (40 mg/kg [Sal-40]), Cur (200 mg/kg [Cur-200]), and Ncur (25 mg/kg [Ncur-25]) groups and exposed to a high-altitude hypobaric hypoxic environment (48 h, 7000 m). Serum-liver enzyme activities (alanine transaminase, aspartate transaminase, and lactate dehydrogenase were detected and histopathology of liver injury was evaluated by hematoxylin and eosin staining, and inflammatory factors were detected in liver tissues by enzyme-linked immunosorbent assays. Pyroptosis-associated proteins (gasdermin D, gasdermin D N-terminal [GSDMD-N], pro-Caspase-1, and cleaved-Caspase-1 [cleaved-Casp1]) and inflammation-associated proteins (nuclear factor-κB [NF-κB], phospho-NF-κB [P-NF-κB], and high-mobility group protein B1 [HMGB1]) levels were analyzed by immunoblotting. Ncur and Cur inhibited increased serum-liver enzyme activities, alleviated liver injury in rats caused by high-altitude hypobaric hypoxic exposure, and downregulated inflammatory factors, including tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and IL-18, in rat liver tissues. The level of P-NF-κB, GSDMD-N, cleaved-Casp1, and HMGB1 in rat liver tissues increased significantly after high-altitude exposure. Ncur and Cur downregulated P-NF-κB, GSDMD-N, cleaved-Casp-1, and HMGB1. Ncur and Cur may inhibit inflammatory responses and pyroptosis in a rat model of high altitude-associated acute liver injury.

Regulated secretion of mutant p53 negatively affects T lymphocytes in the tumor microenvironment.

Several studies have demonstrated the role of the oncogenic mutant p53 in promoting tumor progression; however, there is limited information on the effects of secreted oncogenic mutant p53 on the tumor microenvironment and tumor immune escape. In this study, we found that secretion of mutant p53, determined by exosome content, is dependent on its N-terminal dileucine motif via its binding to ß-adaptin, and inhibited by the CHK2-mediated-Ser 20 phosphorylation. Moreover, we observed that the mutant p53 caused downregulation and dysfunction of CD4+ T lymphocytes in vivo and downregulated the levels and activities of rate-limiting glycolytic enzymes in vitro. Furthermore, inhibition of mutant p53 secretion by knocking down AP1B1 or mutation of dileucine motif could reverse the quantity and function of CD4+ T lymphocytes and restrain the tumor growth. Our study demonstrates that the tumor-derived exosome-mediated secretion of oncogenic mutant p53 inhibits glycolysis to alter the immune microenvironment via functional suppression of CD4+ T cells, which may be the underlying mechanism for tumor immune escape. Therefore, targeting TDE-mediated p53 secretion may serve as a potential therapeutic target for cancer treatment.

Expression profile of microRNAs in patients with decompensated cirrhosis by small RNA deep sequencing.

INTRODUCTION AND OBJECTIVE: Decompensated cirrhosis (DCC) is a more advanced stage of liver cirrhosis (LC). It is important to identify biomarkers to predict DCC progression. The aim of this study was to analyze microRNA (miRNA) profiles of whole blood involved in the DCC process to gain a better understanding of the molecular mechanisms underlying its development. MATERIALS AND METHODS: RNA-Seq analysis of blood samples from a discovery set, including four DCC patients and four LC individuals, was performed to identify differentially expressed miRNAs. The selected differentially expressed miRNAs were validated by using an independent validation set. RESULTS: In this study, a total of 1,036 miRNAs were identified in whole blood samples. Forty differentially expressed miRNAs were identified, including 24 upregulated and 16 downregulated miRNAs. The expression levels of three upregulated miRNAs (hsa-miR-20b-5p, hsa-miR-421, and hsa-miR-1307-3p) and two downregulated miRNAs (hsa-miR-139-5p and hsa-miR-150-5p) were validated by quantitative reverse transcriptase polymerase chain reaction. The receiver operator characteristic curve for the logistic regression model based on hsa-miR-20b-5p, hsa-miR-421, and hsa-miR-150-5p could distinguish DCC patients with excellent diagnostic accuracy (area under the curve: 0.981, p < 0.01). CONCLUSION: The miRNA expression profiles in patients with DCC and LC controls suggested that miR-20b-5p, miR-421, and miR-150-5p could be potential biomarkers and therapeutic targets for this condition.

Simulation of radon detection efficiency with small pulse ionization chamber based on Geant4.

Radon measurement is crucial in assessing the damage to the human body caused by natural radiation. Pulsed ionization chambers are effective for real-time radon measurement and have widespread applications in other radiation techniques. However, due to practical constraints such as limited space and portability concerns, it becomes imperative to consider not only the detection efficiency but also their ease of transportation. This work utilizes the Geant4 Monte Carlo simulation toolkit to characterize the detection models of small cylindrical and flat plate-type pulsed ionization chambers, and carry out a simulation study to analyze the three crucial factors that influence detection efficiency, including the geometry of the chamber, electrode size, and operating temperature. The results indicate that the cylindrical pulse ionization chamber, with a length of 8 cm and radius of 2 cm, has the best detection efficiency and portability in terms of geometric dimensions, achieving a detection efficiency of (58 ± 4)%. Meanwhile, the flat plate pulse ionization chamber, with dimensions of 7 cm in length and 3 cm in width, achieves the best detection efficiency and portability, with a detection efficiency of (54 ± 3)%. In terms of electrode wire size, the cylindrical ionization chamber electrode wire with a length of 7 cm and a radius of 2.5 mm was optimal with a detection efficiency of (59 ± 4)%. In terms of operating temperature, the detection efficiency of the flat-plate pulsed ionization chamber was the highest at 30 °C, which was (58 ± 4)%, and that of the cylindrical pulsed ionization chamber was the highest at 20 °C, which was (63 ± 4)%. By analyzing the influencing factors of the detection efficiency of the pulsed ionization chamber, it has a certain reference value and guiding significance for the research and design of small pulsed ionization chamber detectors for radon measuring instruments.

Atg7 senses ATP levels and regulates AKT1-PDCD4 phosphorylation-ubiquitination axis to promote survival during metabolic stress.

We report that autophagy-related gene 7 (ATG7) modulates p53 activity to regulate cell cycle and survival during metabolic stress, and that indicates Atg7 is functionally involved in cellular homeostasis in autophagy independent fashion. As a protein translation inhibitor, Programmed cell death 4 (PDCD4) expression is regulated by AKT1 phosphorylation. Here, we find that Atg7 interacts with PDCD4 and AKT1 to regulate AKT1-PDCD4 phosphorylation-ubiquitination axis during metabolic stress. We demonstrate that Atg7 senses decrease of ATP levels to suppress AKT-mediated PDCD4 phosphorylation at Ser67, which inhibits PDCD4 ubiquitinating during metabolic stress. Finally, PDCD4 accumulates and functions as a protein translation inhibitor to conserve energy, thus reducing apoptosis and allowing cells to survive stress periods. These results suggest that the ATP-Atg7-PDCD4 axis acts as a metabolic adaptation pathway which dictates cells to overcome metabolic stress.

Drugs targeting TGF-ß/Notch interaction attenuate hypertrophic scar formation by optic atrophy 1-mediated mitochondrial fusion.

Hypertrophic scar (HS) formation is a cutaneous fibroproliferative disease that occurs after skin injuries and results in severe functional and esthetic disability. To date, few drugs have shown satisfactory outcomes for the treatment of HS formation. Transforming growth factor-beta (TGF-ß)/Notch interaction via small mothers against decapentaplegic 3 (Smad3) could facilitate HS formation; therefore, targeting TGF-ß/ Notch interaction via Smad3 is a potential therapeutic strategy to attenuate HS formation. In addition, optic atrophy 1 (OPA1)-mediated mitochondrial fusion contributes to fibroblast proliferation, and TGF-ß/Smad3 axis and the Notch1 pathway facilitate OPA1-mediated mitochondrial fusion. Thus, the aim of this study was to investigate whether drugs targeting TGF-ß/Notch interaction via Smad3 suppressed fibroblast proliferation to attenuate HS formation through OPA1-mediated mitochondrial fusion. We found that the TGF-ß pathway, Notch pathway, and TGF-ß/Notch interaction via Smad3 were inhibited by pirfenidone, the gamma- secretase inhibitor DAPT, and SIS3 in human keloid fibroblasts (HKF) and an HS rat model, respectively. Protein interaction was detected by co-immunoprecipitation, and mitochondrial morphology was determined by electron microscopy. Our results indicated that pirfenidone, DAPT, and SIS3 suppressed the proliferation of HKFs and attenuated HS formation in the HS rat model by inhibiting TGF-ß/Notch interaction via Smad3. Moreover, pirfenidone, DAPT, and SIS3 hindered OPA1-mediated mitochondrial fusion through inhibiting TGF-ß/Notch interaction, thereby suppressing the proliferation of HS fibroblasts and HS formation. In summary, these findings investigating the effects of drugs targeting TGF-ß/Notch interaction on HS formation might lead to novel drugs for the treatment of HS formation.

A safe and effective treatment combination of neoadjuvant therapy and surgical resection for metastatic TFE3-rearranged renal cell carcinoma:a case report.

TFE3-rearranged renal cell carcinoma (RCC) is a rare subtype of renal tumor that primarily affects young women and is characterized by early metastasis and a poor prognosis. This case study presents a 29-year-old woman diagnosed with TFE3-rearranged RCC, who initially presented with painless gross hematuria. Computed Tomography (CT) imaging revealed the presence of a solid mass in the left kidney along with retroperitoneal metastasis. The patient received axitinib, a vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI), as first-line neoadjuvant therapy. Subsequent testing confirmed positive expression of programmed death-1 protein L1 (PDL1), leading to the addition of tislelizumab, a PD1 inhibitor, to the treatment regimen. After 8 months, the patient's tumor size and metastases exhibited significant reduction, providing a favorable opportunity for subsequent surgical intervention. The tumor was classified as IV (pT3aN0M1) based on the pathologic stage of the American Joint Committee on Cancer (AJCC, 8th edition, 2017). The patient achieved long-term survival through combined systemic therapy involving surgery and neoadjuvant treatment. At the 30-month follow-up, there was no evidence of tumor recurrence or metastasis.