Bioactivity evaluation and active compounds identification of Symphoricarpos orbiculatus as potential botanical herbicide.

BACKGROUND: Evaluation of herbicidal activity and identification of active compounds are important bases for the development of new botanical herbicides. RESULTS: This study confirmed that Symphoricarpos orbiculatus has high herbicidal activities against mono-dicotyledonous weeds, including Echinochloa crusgalli, Digitaria sanguinalis, Amaranthus retroflexus and Portulaca oleracea. By bioassay-guided isolation, 12 compounds were isolated and identified from S. orbiculatus for the first time, including iridoids: naucledal (K1), loganin (K2), loganigenin (K3), loganin acid (K4), glucologanin (K5) and vogeloside (K6), as well as flavonoids: quercetine (K7), luteolin (K8), nobiletin (K9), astragalin (K10), isorhamnetin 3-d-glucoside (K11) and rutin (K12). Biological assays showed that iridoids are the main active ingredients of S. orbiculatus. The compounds of K5 and K6 could inhibit both the root (IC50 = 37.54 and 38.91 µg mL-1, respectively) and shoot (IC50 = 42.78 and 45.72 µg mL-1, respectively) of Portulaca oleracea, which have a weeding toxicity similar to that of the commercialized plant-based herbicide pelargonic acid. In addition, the results of pot culture assay showed that S. orbiculatus ethanol extracts had high fresh weight control effect against Digitaria sanguinalis and P. oleracea at the concentration of 40 g L-1. After 7 days, both the soil treatment and the stem and leaf spray method resulted in severe leaf necrosis and significant leaf etiolation. CONCLUSION: Symphoricarpos orbiculatus and its herbicidal active compounds have the potential to develop into botanical herbicides, and are first reported in the present study. © 2024 Society of Chemical Industry.

Identification and validation of a novel necroptosis-related molecular signature to evaluate prognosis and immune features in breast cancer.

Necroptosis has been shown to play an important role in the development of tumors. However, the characteristics of the necroptosis-related subtypes and the associated immune cell infiltration in the tumor microenvironment (TME) of breast cancer (BRCA) remain unclear. In this study, we identified three clusters related to necroptosis using the expression patterns of necroptosis-relevant genes (NRGs), and found that these three clusters had different clinicopathological features, prognosis and immune cell infiltration in the TME. Cluster 2 was characterized by less infiltration of immune cells in the TME and was associated with a worse prognosis. Then, a necroptosis risk score (NRS) composed of 14 NRGs was constructed using the least absolute shrinkage and selection operator regression (LASSO) Cox regression method. Based on NRS, all BRCA patients in the TCGA datasets were classified into a low-risk group and a high-risk group. Patients in the low-risk group were characterized by longer overall survival (OS), lower mutation burden, and higher infiltration level of immune cells in the TME. Moreover, the NRS was significantly associated with chemotherapeutic drug sensitivity. Finally, the knockdown of VDAC1 reduced the proliferation and migration of BRCA cells, and promoted cell death induced by necroptosis inducer. This study identified a novel necroptosis-related subtype of BRCA, and a comprehensive analysis of NRGs in BRCA revealed its potential roles in prognosis, clinicopathological features, TME, chemotherapy, tumor proliferation, and tumor necroptosis. These results may improve our understanding of NRGs in BRCA and provide a reference for developing individualized therapeutic strategies.

TfR Aptamer Enhanced Blood-Brain Barrier Penetration of Biomimetic Nanocomplexes for Intracellular Transglutaminase 2 Imaging and Silencing in Glioma.

Engineering a versatile nanocomplex integrating effective penetration of the blood-brain barrier (BBB), accurate diagnosis, and boosting therapy has always been an intractable challenge in glioblastoma multiforme (GBM). Herein, biomimetic nanocomplexes (TMPsM) for single intracellular transglutaminase 2 (TG2)-triggered self-assembly imaging and RNAi therapy for GBM are subtly developed. To prove the concept, transferrin receptor (TfR) aptamer-modified brain metastatic tumor cell membrane is prepared as the shell for dual BBB targeting capability and prolonged blood retention time. Upon targeting entering into GBM, hollow MnO2 is decomposed to release KKGKGQQ-tetraphenylethene (Pep-TPE) and siRNA. Owing to TG2 dependence, the non-emissive Pep-TPE would be self-aggregated to induce the emission turn-on in GBM that contain overexpressed TG2. The resulting aggregation-induced emission fluorescence imaging with a high signal-to-noise ratio can achieve the precise localization of the tumor and dynamic detection of TG2 activity, thereby allowing the GBM accurate diagnosis. Notably, the TG2 can be silenced by the released siRNA to cause cell apoptosis and increase chemotherapeutic sensitivity, ultimately realizing excellent antitumor efficacy. In vitro and in vivo results demonstrate that the as-prepared TMPsM indeed possess superior BBB penetration, precise diagnosis, and effective therapy of GBM. The proposed strategy may pioneer a new path for the theranostics of brain tumors.

Associations between albumin, globulin, albumin to globulin ratio and muscle mass in adults: results from the national health and nutrition examination survey 2011-2014.

INTRODUCTION: Chronic inflammation and malnutrition play important roles in muscle loss. Although albumin, globulin and albumin to globulin ratio (AGR) are considered to be useful inflammatory-nutritional biomarkers, their relationship with muscle mass remain unclear. This study aimed to investigate the relationship between them in adults. METHODS: We utilized data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 for analysis. Data on albumin, globulin, appendicular skeletal muscle mass, body mass index (BMI) and potential confounders (sociodemographic characteristics, medical conditions, laboratory parameters) were extracted and analyzed. We conducted multivariate linear regression models and smooth curve fittings to investigate the association between albumin, globulin, AGR and muscle mass. Subgroup analysis based on gender and muscle mass were performed. RESULTS: A total of 4110 participants were included, there were 294 participants with low muscle mass (LMM) and 3816 participants with normal muscle mass (NMM). LMM individuals were older, had greater prevalence of diabetes, higher BMI, globulin and triglycerides, lower albumin and AGR. Albumin was positively correlated to muscle mass in men, but negatively correlated with muscle mass in women. There were negative association between globulin and muscle mass, and positive association between AGR and muscle mass among men, but no significant associations were detected among women. Moreover, a linear relationship between albumin, globulin and muscle mass, as well as a non-linear relationship between AGR and muscle mass in men were identified. CONCLUSIONS: The relationships between albumin, globulin, AGR and muscle mass were sex-specific. We speculate these indicators may be useful in assessing muscle mass in men.

Can prophylactic negative pressure wound therapy improve clinical outcomes in spinal fusion surgery? A meta-analysis.

PURPOSE: Recently negative pressure wound therapy (NPWT) is increasingly being prophylactically used to prevent wound complications in various types of surgeries, but its role in spinal fusion surgery was less well established. This study aimed to evaluate the efficacy of prophylactic NPWT (PNPWT) usage in spinal fusion surgery. METHODS: Following PRISMA guidelines, databases PubMed, Embase and Web of Science were searched for relevant studies. Studies comparing PNPWT with standard wound dressing (SWD) were included and analyzed. The primary outcome was the incidence of surgical site infection, and secondary outcomes were incidence of wound dehiscence, overall wound complication, readmission and reoperation. RESULTS: A total of five studies were included; there were 279 patients in PNPWT group and 715 patients in SWD group. Four studies investigated surgical site infection; the pooled analysis showed a significantly lower incidence of surgical site infection in PNPWT group (OR: 0.399; 95% CI: 0.198, 0.802). Two studies explored wound dehiscence, three studies reported overall wound complication, and there were no significant differences between the two groups ((OR: 0.448; 95% CI: 0.144, 1.389) and (OR: 0.562; 95% CI: 0.296, 1.065), respectively). Two studies evaluated readmission, three studies compared reoperation rate, and the pooled results demonstrated no significant difference between the two groups ((OR: 1.045; 95% CI: 0.536, 2.038) and (OR: 0.979; 95% CI: 0.442, 2.169), respectively). CONCLUSIONS: The current evidence suggested PNPWT could effectively reduce postoperative surgical site infection, but it had no significant benefit on reducing the incidence of wound dehiscence, overall wound complication, readmission and reoperation.

A real-time 3D electromagnetic navigation system for percutaneous pedicle screw fixation in traumatic thoraco-lumbar fractures: implications for efficiency, fluoroscopic time, and accuracy compared with those of conventional fluoroscopic guidance.

PURPOSE: Navigation is becoming more useful in percutaneous pedicle screw fixation (PPSF). The aim of this study was to compare the efficiency, fluoroscopic time, accuracy, and clinical outcomes of PPSF with a novel electromagnetic navigation (EMN) system for thoraco-lumbar (TL) fractures with those of PPSF with conventional C-arm fluoroscopic (CF) guidance. METHODS: A retrospective study was conducted. A total of 162 screws were implanted in 29 patients with the assistance of the EMN system (EMN group), and 220 screws were inserted in 40 patients by using CF guidance (CF group). The duration of surgery, placement time per screw, fluoroscopic time per screw, accuracy of pedicle screw placement, and clinical outcomes were compared between the two groups. RESULTS: The duration of surgery and placement time per screw in the EMN group were significantly lower than those in the CF group (P < 0.05). The fluoroscopic time per screw in the CF group was significantly longer than that in the EMN group (P < 0.05). The learning curve of PPSF in the EMN group was steeper than that in the CF group. The accuracy of pedicle screw placement in the EMN group was more precise than that in the CF group (P < 0.05). The VAS scores in the EMN group were significantly lower than those in the CF group at one-week postoperatively (P < 0.05). CONCLUSION: Compared with PPSF by using conventional fluoroscopic guidance, PPSF with the aid of the EMN system can increase the efficiency and accuracy of pedicle screw placement and reduce the fluoroscopic time.

A real-time 3D electromagnetic navigation system for percutaneous transforaminal endoscopic discectomy in patients with lumbar disc herniation: a retrospective study.

BACKGROUND: In this study, we present a novel electromagnetic navigation (EMN) system for percutaneous transforaminal endoscopic discectomy (PTED) procedure. The objective of this study was to investigate the safety and effectiveness of the PTED with the assistance of the EMN system and compare it with the conventional PTED with the assistance of fluoroscopic guidance (C-arm). METHODS: The clinical data of 79 patients (32 in EMN group and 47 in C-arm group) undergoing PTED for lumbar disc herniation (LDH) from January to September of 2019 were analyzed retrospectively. The radiation time, puncture time, operation time, visual analog scale (VAS), Oswestry disability index (ODI), modified MacNab criteria, and radiological parameters were recorded in both groups. RESULTS: Radiation time, puncture time, and operation time were significantly reduced in the EMN group compared with the C-arm group (P < 0.05). Compared with the C-arm group, a steeper learning curve was observed in the EMN group. There were no significant differences between the two groups regarding VAS and ODI scores at different time points (P > 0.05). The satisfaction rates of the EMN and C-arm groups were 90.63 and 87.23%, respectively, but no significant difference was found between the two groups (P > 0.05). There was no significant difference regarding translation and angular motion between the two groups at preoperation and postoperation (P > 0.05). CONCLUSIONS: The EMN system can be applied to facilitate the PETD procedure. It can significantly reduce the intraoperative radiation time, puncture time, and operation time, and reshape the learning curve of PTED. Due to limitations of a retrospective study, results may need validation with larger prospective randomized clinical trials.

Assessment of clinical, imaging, surgical risk factors for subsequent fracture following vertebral augmentation in osteoporotic patients.

INTRODUCTION: Currently, the risk factors for subsequent fracture following vertebral augmentation remain incomplete and controversial. To provide clinicians with accurate information for developing a preventive strategy, we carried out a comprehensive evaluation of previously controversial and unexplored risk factors. METHODS: We retrospectively reviewed patients with osteoporotic vertebral compression fracture in lumbar spine who received vertebral augmentation between January 2019 and December 2020. Based on whether refracture occurred, patients were assigned to refracture and non-refracture group. The clinical characteristics, imaging parameters (severity of vertebral compression, spinal sagittal alignment, degeneration of paraspinal muscles), and surgical indicators (cement distribution and leakage, correction of spinal sagittal alignment) were collected and analyzed. RESULTS: There were 128 patients and 16 patients in non-refracture and refracture group. The incidence of previous fracture, multiple fractures, and cement leakage were notably higher, relative cross-sectional area of psoas (r-CSAPS) was significantly smaller, CSA ratio, fatty infiltration of erector spinae plus multifidus (FIES+MF), FIPS, postoperative lumbar lordosis (post-LL), correction of body angel (BA), and LL were significantly greater in refracture group. Binary logistic regression analysis revealed previous fracture, cement leakage, post-LL, and correction of BA were independent risk factors. According to the ROC curve, correction of BA showed the highest prediction accuracy, and the critical value was 3.45°. CONCLUSIONS: The occurrence of subsequent fracture might be the consequence of multiple factors. Previous fracture, cement leakage, post-LL, and correction of BA were identified as independent risk factors. Furthermore, the correction of BA should not exceed 3.45°, especially in patients with risk factors.

Three-dimensional high-definition exoscope (Kestrel View II) in anterior cervical discectomy and fusion: a valid alternative to operative microscope-assisted surgery.

BACKGROUND: Operative microscope (OM) has greatly advanced modern spine surgery, but remains limited by several drawbacks. Therefore, a three-dimensional (3D) high-definition (HD) exoscope (EX) (Kestrel View II, Mataka Kohli, Japan) system has been developed and used as an alternative to the OM. The aim of this study was to assess and compare the perioperative data and clinical outcomes of anterior cervical discectomy and fusion (ACDF) procedure with either an EX or OM. METHODS: Forty-eight patients with cervical spondylotic myelopathy (CSM) underwent ACDF assisted by the EX or OM between January 2019 and December 2019. We collected and compared data on operative time, intraoperative bleeding, postoperative hospitalization stay, complications, and clinical outcomes between the two groups. The clinical outcomes were evaluated by using visual analogue scale (VAS) scores, Japanese Orthopedic Association (JOA) scores, the recovery rate of JOA scores, and Odom criteria. RESULTS: The operative time in the EX group was significantly shorter than that in the OM group (P < 0.05). The VAS and JOA scores were significantly improved in both groups after surgery (P < 0.05). In addition, the VAS scores in the EX group were significantly lower than those in the OM group at 1 week postoperatively (P < 0.05). The good-to-excellent outcome rates were 90.48 and 88.89% in the EX group and OM group, respectively, whereas the complication occurrence rates of the EX group and OM group were 4.76 and 11.11%, respectively. CONCLUSIONS: EX-assisted and OM-assisted ACDF resulted in similar clinical outcomes for CSM, while EX-assisted surgery may be related to a short operative time and fewer complications.

Clinical outcomes of transforaminal endoscopic lateral recess decompression by using the visualized drilled foraminoplasty and visualized reamed foraminoplasty: a comparison study.

BACKGROUND: Lateral recess stenosis (LRS) is a common degenerative disease in the elderly. Since the rise of comorbidity is associated with increasing age, transforaminal endoscopic lateral recess decompression (TE-LRD) is advocated. The objective of this study was to compare the clinical outcomes of TE-LRD in patients with LRS via visualized drilled foraminoplasty (VDF) or visualized reamed foraminoplasty (VRF) technique. METHODS: A total of 45 and 42 consecutive patients with limp or unilateral radiculopathy symptoms underwent TE-LRD using the VDF and VRF technique, respectively. The radiation exposure and operation time, time to return to work, and complications were compared between two groups. Their clinical outcomes were evaluated with the visual analogue scale (VAS) leg pain score, VAS back pain score, Oswestry Disability Index (ODI) and modified MacNab's criteria. RESULTS: The average values of radiation exposure and operative time in the VDF group were significantly higher than those in the VRF group (P <  0.05). The postoperative VAS and ODI scores in both groups were significantly improved compared with those before the operation (P <  0.05). In addition, the VAS score of the leg pain and ODI score in the VRF group were significantly lower than those in the VDF group at the 1-week follow-up (P <  0.05). The good-to-excellent rates of the VDF group and VRF group were 88.89 and 90.48%, respectively, whereas the complication occurrence rates were 6.67 and 4.76% in the VDF group and VRF group, respectively. CONCLUSIONS: TE-LRD performed by using VRF technique can be applied to treat LRS safely and effectively with short radiation exposure and operation time. This technique was comparable to the VDF technique with improved VAS leg pain and ODI scores in the short period after the operation. However, potential complications and risks still need to be considered.

Assessment of surface water quality using a growing hierarchical self-organizing map: a case study of the Songhua River Basin, northeastern China, from 2011 to 2015.

The analysis of a large number of multidimensional surface water monitoring data for extracting potential information plays an important role in water quality management. In this study, growing hierarchical self-organizing map (GHSOM) was applied to a water quality assessment of the Songhua River Basin in China using 22 water quality parameters monitored monthly from 13 monitoring sites from 2011 to 2015 (14,782 observations). The spatial and temporal features and correlation between the water quality parameters were explored, and the major contaminants were identified. The results showed that the downstream of the Second Songhua River had the worst water quality of the Songhua River Basin. The upstream and midstream of Nenjiang River and the Second Songhua River had the best. The major contaminants of the Songhua River were chemical oxygen demand (COD), ammonia nitrogen (NH3-N), total phosphorus (TP), and fecal coliform (FC). In the Songhua River, the water pollution at downstream has been gradually eased in years. However, FC and biochemical oxygen demand (BOD5) showed growth over time. The component planes showed that three sets of parameters had positive correlations with each other. GHSOM was found to have advantages over self-organizing maps and hierarchical clustering analysis as follows: (1) automatically generating the necessary neurons, (2) intuitively exhibiting the hierarchical inheritance relationship between the original data, and (3) depicting the boundaries of the classification much more clearly. Therefore, the application of GHSOM in water quality assessments, especially with large amounts of monitoring data, enables the extraction of more information and provides strong support for water quality management.

Phosphatidylserine on blood cells and endothelial cells contributes to the hypercoagulable state in cirrhosis.

BACKGROUND & AIMS: The mechanism of thrombogenicity in cirrhosis is largely unknown. Our objective was to study the relationship between phosphatidylserine on blood cells and endothelial cells and the hypercoagulable state in cirrhotic patients. METHODS: Patients with cirrhosis and healthy controls were studied. Lactadherin was used to quantify phosphatidylserine exposure on blood cells and endothelial cells. Procoagulant activity of cells was evaluated using clotting time and purified coagulation complex assays. Fibrin production was determined by turbidity. Phosphatidylserine exposure, fibrin strands and FVa/Xa binding on cells were observed using confocal microscopy. RESULTS: Our study showed that phosphatidylserine exposure on erythrocytes, platelets and leucocytes in cirrhotic patients increased progressively with Child-Pugh categories. In addition, we found that endothelial cells treated with cirrhotic serum in vitro exposed more phosphatidylserine than those exposed to healthy serum. The exposed phosphatidylserine supported a shorter coagulation time and increased FXa, thrombin and fibrin formation. Notably, phosphatidylserine+ erythrocytes also promoted shorter coagulation times and more fibrin generation in cirrhotic microparticle-depleted plasma, regardless of Child-Pugh categories. Confocal microscopy data showed that the FVa/FXa complex and fibrin fibrils colocalized with phosphatidylserine on endothelial cells. Lactadherin significantly inhibited FXa and thrombin generation and consequently decreased fibrin production in normal or cirrhotic plasma. CONCLUSIONS: These results lead us to believe that exposed phosphatidylserine on activated or injured erythrocytes, platelets, leucocytes and endothelial cells plays an important role in the hypercoagulable state in cirrhotic patients. Thus, blocking phosphatidylserine binding sites might be a new therapeutic target for preventing thrombosis.

Increased phosphatidylserine-exposing microparticles and their originating cells are associated with the coagulation process in patients with IgA nephropathy.

BACKGROUND: Relatively little information is available about phosphatidylserine positive (PS(+)) microparticles (MPs) and their originating cells in IgA nephropathy (IgAN) despite well-established intraglomerular coagulation. Our objectives were to detect PS exposure on MP membranes and MP-origin cells and to evaluate its role in procoagulant activity (PCA) and fibrin formation and their association with pathological lesions in the disease. METHODS: Patients with IgAN and healthy controls were studied. Lactadherin was used to quantify PS exposure on MPs and MP-origin cells. PCA of MPs and MP-origin cells was evaluated by clotting time and purified coagulation complex assays. Fibrin production was determined by turbidity. PS exposure, fibrin strands and FVa/Xa binding were observed on MPs/cells using confocal microscopy. RESULTS: Using flow cytometry, we found that IgAN patients had high levels of PS(+) MPs derived from lymphocytes, monocytes, neutrophils, platelets, erythrocytes and endothelial cells (ECs). The PS exposure on MP-origin cells also increased in these patients. MPs and MP-origin cells (leukocytes, platelets and erythrocytes) isolated from IgAN patients and ECs cultured with IgAN serum had a significantly shorter median coagulation time (P < 0.001), higher median intrinsic FXa (P < 0.001) and higher thrombin (P < 0.001) generation than controls. These coagulation functional assays were associated with the glomerular lesions. The lesions were also correlated with glomerular fibrin deposition (all P < 0.05). In the presence of patient MPs or their related cells, fibrin formation peaked faster with a higher maximum turbidity when compared with healthy controls. Blocking PS with lactadherin in the IgAN group prolonged coagulation time to control levels, inhibited the PCA up to 80% and markedly reduced fibrin formation. More importantly, we observed that fibrin strands formed on MPs and ECs in the same regions that bound lactadherin, similar to the FVa/Xa costaining. CONCLUSIONS: We find that high levels of PS(+) MPs and the MP-origin cells are associated with the coagulation process in IgAN, and this may provide a previously unrecognized contribution to intraglomerular coagulation.

[Application of Nice knot technique in wound closure of Gustilo type â ¢A and â ¢B open tibial fractures].

Objective: To explore the effectiveness of Nice knot technique for wound closure in Gustilo type ⅢA and ⅢB open tibial fractures. Methods: A retrospective study was performed on 22 patients with Gustilo type ⅢA and ⅢB open tibial fractures, who underwent wound closure using the Nice knot technique and were admitted between June 2021 and June 2022. There were 15 males and 7 females. The age ranged from 18 to 67 years, with an average of 41.9 years. The causes of injury included traffic accident in 11 cases, falling from height in 7 cases, and heavy object injuries in 4 cases. Fractures were located on the left side in 9 cases and on the right side in 13 cases. And 9 cases were type ⅢA fractures and 13 were type ⅢB fractures according to Gustilo classification. All patients had extensive soft tissue injuries, and no vascular or neurological damage was observed. The time from injury to debridement was 3-8 hours (mean, 6.5 hours). The sizes of wounds before operation and at 2 weeks after operation were measured and wound healing rate at 2 weeks after operation were calculated. The wound healing time and wound healing grading were recorded. The Vancouver Scar Scale (VSS) score was used to assess the wound scar after wound healed and the excellent and good rate was calculated. Results: The wound area was 21.0-180.0 cm 2 (mean, 57.82 cm 2) before operation, and it was 1.2-27.0 cm 2 (mean, 6.57 cm 2) at 2 weeks after operation. The wound healing rate at 2 weeks after operation was 76%-98% (mean, 88.6%). After operation, 2 cases needed to adjust Nice knot due to skin cutting and 1 case occurred soft tissue infection on the wound. The other patient's wounds healed. The average wound healing time was 27.8 days (range, 18-44 days). And the wound healing were grade A in 13 cases and grade B in 9 cases. VSS score was 2-9, with an average of 4.1; 10 cases were rated as excellent, 10 as good, and 2 as poor, with an excellent and good rate of 90.9%. All patients were followed up 9-24 months (mean, 14.6 months). During follow-up, no deep infection or osteomyelitis occurred. Two cases experienced fracture non-union, and were treated with compression fixation and bone grafting. The fractures of the other patients all healed, with a healing time of 85-190 days (mean, 148.2 days). Conclusion: Nice knot technique can be used in wound closure of Gustilo type ⅢA and ⅢB open tibial fractures effectively, which is easy to operate.

Roles of mechanosensitive ion channel PIEZO1 in the pathogenesis of brain injury after experimental intracerebral hemorrhage.

Secondary brain injury after intracerebral hemorrhage (ICH) is the main cause of poor prognosis in ICH patients, but the underlying mechanisms remain less known. The involvement of Piezo1 in brain injury after ICH was studied in a mouse model of ICH. ICH was established by injecting autologous arterial blood into the basal ganglia in mice. After vehicle, Piezo1 blocker, GsMTx4, Piezo1 activator, Yoda-1, or together with mannitol (tail vein injection) was injected into the left lateral ventricle of mouse brain, Piezo1 level and the roles of Piezo1 in neuronal injury, brain edema, and neurological dysfunctions after ICH were determined by the various indicated methods. Piezo1 protein level in neurons was significantly upregulated 24 h after ICH in vivo (human and mice). Piezo1 protein level was also dramatically upregulated in HT22 cells (a murine neuron cell line) cultured in vitro 24 h after hemin treatment as an in vitro ICH model. GsMTx4 treatment or together with mannitol significantly downregulated Piezo1 and AQP4 levels, markedly increased Bcl2 level, maintained more neurons alive, considerably restored brain blood flow, remarkably relieved brain edema, substantially decreased serum IL-6 level, and almost fully reversed the neurological dysfunctions at ICH 24 h group mice. In contrast, Yoda-1 treatment achieved the opposite effects. In conclusion, Piezo1 plays a crucial role in the pathogenesis of brain injury after ICH and may be a target for clinical treatment of ICH.

Hollow Cu2MoS4 nanoparticles loaded with immune checkpoint inhibitors reshape the tumor microenvironment to enhance immunotherapy for pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease that responds poorly to single-drug immunotherapy with PD-L1 (CD274) inhibitors. Here, we prepared mesoporous nanomaterials Cu2MoS4 (CMS)/PEG loaded with PD-L1 inhibitor BMS-1 and CXCR4 inhibitor Plerixafor to form the nanodrug CMS/PEG-B-P. In vitro experiments, CMS/PEG-B-P have a more substantial inhibitory effect on the expression of PD-L1 and CXCR4 as well as to promote the apoptosis of pancreatic cancer cells KPC and suppressed KPC cell proliferation were detected by flow cytometry, qPCR and Western blotting (WB). Promotes the release of the cytotoxic substance reactive oxygen species (ROS) and the production of the immunogenic cell death (ICD) marker calreticulin (CRT) in KPC cells. CMS/PEG-B-P was also detected to have a certain activating effect on mouse immune cells, dendritic cells (mDC) and macrophage RAW264.7. Subcutaneous tumorigenicity experiments in C57BL/6 mice verified that CMS/PEG-B-P had an inhibitory effect on the growth of tumors and remodeling of the tumor immune microenvironment, including infiltration of CD4+ and CD8+ T cells and polarization of macrophages, as well as reduction of immunosuppressive cells. Meanwhile, CMS/PEG-B-P was found to have different effects on the release of cytokines in the tumor immune microenvironment, including The levels of immunostimulatory cytokines INF-γ and IL-12 are increased and the levels of immunosuppressive cytokines IL-6, IL-10 and IFN-α are decreased. In conclusion, nanomaterial-loaded immune checkpoint inhibitor therapies can enhance the immune response and reduce side effects, a combination that shows great potential as a new immunotherapeutic approach. STATEMENT OF SIGNIFICANCE: Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease that has a low response to single-drug immunotherapy with PD-L1 (CD274) inhibitors. We preared PEG-modified mesoporous nanomaterials Cu2MoS4 (CMS) loaded with PD-L1 inhibitor BMS-1 and CXCR4 inhibitor Plerixafor to form the nanodrug CMS/PEG-B-P. Our study demonstrated that Nanomaterial-loaded immune checkpoint inhibitor therapies can enhance the immune response and reduce side effects, a combination that shows great potential as a new immunotherapeutic approach.

SECTM1 promotes the development of glioblastoma and mesenchymal transition by regulating the TGFß1/Smad signaling pathway.

Objective: Secreted and transmembrane protein 1 (SECTM1) is a gene encoding a transmembrane protein. The role of SECTM1 in glioblastoma (GBM) is unclear. Here, we reported the abnormal expression of SECTM1 in GBM for the first time and studied the role and mechanism of SECTM1 in GBM. Methods: qRT-PCR, Western blotting and immunofluorescence were used to detect the expression of SECTM1 in gliomas of different grades and GBM cell lines. After the knockdown of SECTM1 expression in cell lines by shRNA, the effect of SECTM1 in GBM cell lines was verified by CCK-8, Transwell, EdU and wound healing experiments. We further investigated the effect and mechanism of SECTM1 on GBM in vitro and in vivo. The effect of SECTM1 on glioma growth was detected by subcutaneous tumor xenografts in nude mice in vivo. Results: The results showed that the knockdown of SECTM1 expression in cell lines significantly inhibited the proliferation, migration and invasion of GBM cells while inhibiting the progression of subcutaneous xenograft tumors in nude mice. However, the role and molecular mechanism of SECTM1 in GBM remain unclear. SECTM1 was found to promote GBM epithelial-mesenchymal transition (EMT) like processes. Bioinformatics analysis and Western blotting showed that SECTM1 regulates glioblastoma invasion and EMT-like processes mainly through the TGFß1/Smad signaling pathway. Conclusion: The low expression of SECTM1 has an inhibitory effect on GBM and is a potential target for GBM treatment. SECTM1 may also be a promising biomarker for the diagnosis and prognosis of GBM.

Multi-omic profiling of clear cell renal cell carcinoma identifies metabolic reprogramming associated with disease progression.

Clear cell renal cell carcinoma (ccRCC) is a complex disease with remarkable immune and metabolic heterogeneity. Here we perform genomic, transcriptomic, proteomic, metabolomic and spatial transcriptomic and metabolomic analyses on 100 patients with ccRCC from the Tongji Hospital RCC (TJ-RCC) cohort. Our analysis identifies four ccRCC subtypes including De-clear cell differentiated (DCCD)-ccRCC, a subtype with distinctive metabolic features. DCCD cancer cells are characterized by fewer lipid droplets, reduced metabolic activity, enhanced nutrient uptake capability and a high proliferation rate, leading to poor prognosis. Using single-cell and spatial trajectory analysis, we demonstrate that DCCD is a common mode of ccRCC progression. Even among stage I patients, DCCD is associated with worse outcomes and higher recurrence rate, suggesting that it cannot be cured by nephrectomy alone. Our study also suggests a treatment strategy based on subtype-specific immune cell infiltration that could guide the clinical management of ccRCC.

The prognostic impact of tumor location in non-muscle-invasive bladder cancer patients undergoing transurethral resection: insights from a cohort study utilizing chinese multicenter and SEER registries.

OBJECTIVE: Most bladder cancers are non-muscle invasive bladder cancer (NMIBC), and transurethral resection of bladder tumors (TURBT) is the standard treatment. However, postoperative recurrence remains a significant challenge, and the influence of bladder tumor location on prognosis is still unclear. This study aims to investigate how tumor location affects the prognosis of NMIBC patients undergoing TURBT and to identify the optimal surgical approach. METHODS: A multicenter study was conducted, which included Chinese NMIBC data from 15 hospitals (1996-2019) and data from 17 registries of the Surveillance, Epidemiology, and End Results database (SEER) (2000-2020). Patients initially diagnosed with NMIBC and undergoing TURBT or partial cystectomy were analyzed, with cases lost to follow-up or with missing data excluded. The study investigated the overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) among patients with different tumor locations. Kaplan-Meier, Cox regression, and propensity score matching methods were employed to explore the association between tumor location and prognosis. Stratified populations were analyzed to minimize bias. RESULTS: This study included 118,477 NMIBC patients and highlighted tumor location as a crucial factor impacting post-TURBT prognosis. Both anterior wall and dome tumors independently predicted adverse outcomes in two cohorts. For anterior wall tumors, the Chinese cohort showed hazard ratios (HR) for OS of 4.35 (P < 0.0001); RFS of 2.21 (P < 0.0001); SEER cohort OS HR of 1.10 (P = 0.0001); DSS HR of 1.13 (P = 0.0183). Dome tumors displayed similar trends (Chinese NMIBC cohort OS HR of 7.91 (P < 0.0001); RFS HR of 2.12 (P < 0.0001); SEER OS HR of 1.05 (P = 0.0087); DSS HR of 1.14 (P = 0.0006)). Partial cystectomy significantly improved the survival of dome tumor patients compared to standard TURBT treatment (P < 0.01). CONCLUSION: This study reveals the significant impact of tumor location in NMIBC patients on the outcomes of TURBT treatment, with tumors in the anterior wall and bladder dome showing poor post-TURBT prognosis. Compared to TURBT treatment, partial cystectomy improves the prognosis for bladder dome tumors. This study provides guidance for personalized treatment and prognosis management for NMIBC patients.

[Percutaneous hollow screw internal fixation combined with cementoplasty in treatment of periacetabular metastasis].

Objective: To explore the percutaneous hollow screw internal fixation combined with cementoplasty in the treatment of periacetabular metastasis. Methods: A retrospective study was performed on 16 patients with periacetabular metastasis who were treated with percutaneous hollow screw internal fixation combined with cementoplasty between May 2020 and May 2021. There were 9 males and 7 females. The age ranged from 40 to 73 years, with an average of 53.6 years. The tumor involved around the acetabulum, and 6 cases were located on the left and 10 cases on the right. Operation time, frequency of fluoroscopy, bed rest time, and complications were recorded. Before operation, and at 1 weeks, 3 months after operation, the visual analogue scale (VAS) score was used to evaluate the pain degree, the short-form 36 health survey scale (SF-36) score was used to evaluate the quality of life. At 3 months after operation, the Musculoskeletal Tumor Society (MSTS) scoring system was used to evaluate the functional recovery of patients. During follow-up, the loosening of internal fixator and bone cement leakage were observed by X-ray film. Results: All patients were performed operation successfully. The operation time ranged from 57 to 82 minutes, with an average of 70.4 minutes. The frequency of intraoperative fluoroscopy was 16-34 times, with an average of 23.1 times. After operation, 1 case of incision hematoma and 1 case of scrotal edema occurred. All patients felt the pain relieved after operation. The patients started walking at 1-3 days after operation, with an average of 1.4 days. All patients were followed up 6-12 months (mean 9.7 months). The VAS and SF-36 scores significantly improved after operation when compared with the preoperative scores, and the scores at 3 months after operation were significant better than those at 1 week after operation ( P<0.05). At 3 months after operation, the MSTS score ranged from 9 to 27, with an average of 19.8. Among them, 3 cases were excellent (18.75%), 8 cases were good (50%), 3 cases were fair (18.75%), and 2 cases were poor (12.5%). The excellent and good rate was 68.75%. And 11 patients returned to normal walking, 3 had mild claudication, and 2 had obvious claudication. Radiological examination showed that there were 2 cases of bone cement leakage after operation, and there was no internal fixator loosening or displacement. Conclusion: Percutaneous hollow screw internal fixation combined with cementoplasty can effectively relieve pain and improve the quality of life of patients with periacetabular metastasis.