Uncovering the mechanisms of diosmin in treating obesity-related kidney injury based on network pharmacology, molecular docking, and in vitro validation.

Obesity increases the risk of kidney injury, involving various pathological events such as inflammation, insulin resistance, lipid metabolism disorders, and hemodynamic changes, making it a significant risk factor for the development and progression of chronic kidney disease. Diosmin, a natural flavonoid glycoside, exhibits anti-inflammatory, antioxidant, anti-lipid, and vasodilatory effects. However, whether diosmin has a protective effect on obesity-related kidney injury remains unclear. The molecular formula of diosmin was obtained, and diosmin and target genes related to obesity-related kidney injury were screened. The interaction between overlapping target genes was analyzed. GO functional enrichment and KEGG pathway enrichment analyses were performed on overlapping target genes. Molecular docking was employed to assess the binding strength between overlapping target genes. Palmitic acid-induced damage to HK-2 cells, which were then treated with diosmin. Subsequently, the expression levels of relevant mRNAs and proteins were measured. Network analysis identified 219 potential diosmin target genes, 6800 potential target genes related to obesity-related kidney injury, and 93 potential overlapping target genes. Protein-protein interaction networks and molecular docking results revealed that AKT1, TNF-α, SRC, EGFR, ESR1, CASP3, MMP9, PPAR-γ, GSK-3ß, and MMP2 were identified as key therapeutic targets, and they exhibited stable binding with diosmin. GO analysis indicated that these key targets may participate in inflammation, chemical stress, and protein phosphorylation. KEGG revealed that pathways in cancer, AGE-RAGE signaling pathway, PI3K-AKT signaling pathway, PPAR signaling pathway, and insulin resistance as crucial in treating obesity-related kidney injury. CCK-8 assay showed that diosmin significantly restored the viability of HK-2 cells affected by palmitic acid. Oil Red O staining demonstrated that diosmin significantly improved lipid deposition in HK-2 cells induced by palmitic acid. PCR results showed that diosmin inhibited the mRNA levels of AKT1, TNF-α, EGFR, ESR1, CASP3, MMP9, GSK-3ß, and MMP2 while promoting the mRNA level of PPAR-γ. Western blot analysis revealed that diosmin restored PPAR-γ protein expression, inhibited NF-kB p-p65 protein expression, and reduced TNF-α protein expression. Diosmin demonstrated multi-target and multi-pathway effects in the treatment of obesity-associated renal injury, with key targets including AKT1, TNF-α, EGFR, ESR1, CASP3, MMP9, PPAR-γ, GSK-3ß, and MMP2. The mechanism may be through the modulation of the PPAR-γ/NF-κB signaling pathway, which can attenuate inflammatory responses and protect the kidney.

Reduced-dose chemotherapy and blinatumomab as induction treatment for newly diagnosed Ph-negative B-cell precursor acute lymphoblastic leukemia: a phase 2 trial.

Blinatumomab has emerged as a promising component of first-line therapy for acute B-cell precursor lymphoblastic leukemia (BCP-ALL), bolstering treatment efficacy. To mitigate CD19 selection pressure and reduce the incidence of blinatumomab-associated toxicities, pre-treatment chemotherapy is recommended before administering blinatumomab. From September 2022 to December 2023, we conducted a single-arm, multicenter, phase 2 trial (NCT05557110) in newly diagnosed Philadelphia chromosome-negative BCP-ALL (Ph-negative BCP-ALL) patients. Participants received induction treatment with reduced-dose chemotherapy (RDC), comprising idarubicin, vindesine, and dexamethasone over 7 days, followed by 2 weeks of blinatumomab. Those failing to achieve composite complete remission (CRc) received an additional 2 weeks of blinatumomab. The primary endpoint was the CRc rate post initial induction treatment. Of the 35 enrolled patients, 33 (94%) achieved CRc after 2 weeks of blinatumomab, with 30 (86%) achieving measurable residual disease (MRD) negativity. Two patients extended blinatumomab to 4 weeks. With either 2 or 4 weeks of blinatumomab treatment, all patients achieved CR (35/35) and 89% (31/35) were MRD negativity. The median time to CR was 22 days. Immune effector cell-associated neurotoxicity syndrome was limited (14%, all grade 1). Non-hematological adverse events of grade 3 or higher included pneumonia (17%), sepsis (6%), and cytokine release syndrome (9%). With a median follow-up of 11.5 months, estimated 1-year overall survival and 1-year progression-free survival rates were 97.1% and 82.2%, respectively. These findings affirm that RDC followed by blinatumomab is an effective and well-tolerated induction regimen for newly diagnosed Ph-negative BCP-ALL, supporting a shift towards less intensive and more targeted therapeutic approaches. Trial registration: https://www.clinicaltrials.Gov . Identifier NCT05557110.

Association analyses between urinary concentrations of multiple trace elements and gastric precancerous lesions and gastric cancer in Anhui province, eastern China.

Background: Limited epidemiological evidence suggests that exposure to trace elements adversely impacts the development of gastric precancerous lesions (GPL) and gastric cancer (GC). This study aimed to estimate the association of individual urinary exposure to multiple elements with GPL and GC. Methods: A case-control investigation was conducted in Anhui Province from March 2021 to December 2022. A total of 528 subjects (randomly sampled from 1,020 patients with GPL, 200 patients with GC, and 762 normal controls) were included in our study. Urinary levels of iron (Fe), copper (Cu), zinc (Zn), nickel (Ni), strontium (Sr), and Cesium (Cs) were measured using inductively coupled plasma mass spectrometry (ICP-MS). Four different statistical approaches were employed to explore the risk of GPL and GC with mixed exposure, including multivariate logistic regression, weighted quantile regression (WQS), quantile g-computation (Qgcomp), and the Bayesian kernel machine regression (BKMR) model. Results: The WQS model indicated that urinary exposure to a mixture of elements is positively correlated with both GPL and GC, with ORs for the mixture exposure of 1.34 (95% CI: 1.34-1.61) for GPL and 1.38 (95% CI: 1.27-1.50) for GC. The Qgcomp and BKMR models also demonstrated a statistically significant positive correlation between the mixture and both GPL and GC. Conclusion: Considering the limitations of case-control studies, future prospective studies are warranted to elucidate the combined effects and mechanisms of trace elements exposure on human health.

Cordycepin ameliorates kidney injury by inhibiting gasdermin D-mediated pyroptosis of renal macrophages through nuclear factor kappa-B.

To explain the effect and mechanism of cordycepin (COR) in resisting acute kidney injury (AKI). Network pharmacology was employed to analyze the correlations between COR, AKI, and pyroptosis, as well as the action target of COR. A mouse model of AKI was established by ischemia reperfusion injury (IRI), and after treatment with COR, the renal function, tissue inflammatory cytokine levels, and pyroptosis-related signals were detected in mice. In in-vitro experiments, damage of renal macrophages was caused by the oxygen-glucose deprivation model, and pyroptosis indicators and inflammatory cytokine levels were assayed after COR treatment. Network pharmacological analysis revealed that nuclear factor kappa-B (NF-κB) was the primary action target of COR and that COR could inhibit kidney injury and tissue inflammation during IRI by inhibiting NF-κB-mediated gasdermin D cleavage. When NF-κB was inhibited, the effect of COR was weakened. COR in renal macrophages could inhibit pyroptosis and lower the levels of inflammatory cytokines, whose effect was associated with NF-κB. Our study finds that COR can play an anti-inflammatory role and inhibit the progression of AKI through the NF-κB-mediated pyroptosis, which represents its nephroprotective mechanism.

Discrete Macrocyclic Polymers Hosts Induced Cascade Luminescence Enhancement and Application in Bioimaging.

The integration of polymers, supramolecular macrocycles and aggregation-induced emission (AIE) molecules provides numerous possibilities for constructing various functional supramolecular systems. Herein, we constructed supramolecular assembled systems based on discrete macrocyclic polymer hosts via the cooperation of hydra-headed macrocycles containing two or three pillar[5]arene units (defined as P2, P3), the block polymer F127 and AIE molecules (alkyl-cyano modified tetraphenylethene, alkyl-triazole-cyano modified 9,10-distyrylanthracene, defined as TPE-(CN)4 and DSA-(TACN)2). Compared with the binary assembly between hydra-headed hosts or F127 and AIE molecules, cascaded supramolecular assembly-induced emission enhancement (SAIEE) in aqueous solution was achieved in discrete macrocyclic polymer-based supramolecular assembled systems. Considering the cascaded SAIEE performance, we have successfully applied discrete macrocyclic polymer-based supramolecular assembled systems to bioimaging and constructed an artificial light-harvesting system (LHs) to explore more potential applications. The supramolecular assembly form of discrete macrocyclic polymers hosts and AIE molecules proposed in this work provides new inspiration for the construction and application of high-performance supramolecular luminescent systems.

Application of microdialysis combined with lipidomics to analyze fatty acid metabolic changes in the disease process of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a metabolically active disease, with shifts in fatty acid metabolism during disease progression profoundly affecting the systemic inflammatory response. Altered fatty acid biomarker metabolism may be a key target for the treatment of RA. To investigate the changes of fatty acid metabolism in RA, collagen-induced arthritis (CIA) model was established. Microdialysis sampling was utilized to overcome the characteristic of occlusive joint cavity in vivo synovial fluid (SF) sampling. Lipidomic methods were established with the UHPLC-Orbitrap Exploris120 platform, and lipid measurements were performed on serum and SF samples. Then, multivariate statistical analyses were performed to detect changes in lipid metabolites induced by CIA. Consequently, a total of 22 potential biomarkers associated with differential fatty acids were screened and identified in serum, and 13 were identified in SF. Notably, alterations were observed in metabolites such as Hexadecanoic acid, Octadecanoic acid, Arachidonic acid, (+/-)11,12-EpETrE, DHA, DPA, Myristic acid, Suberic acid, and others. This study explored a new mechanism of the RA disease process from the perspective of fatty acid metabolism. It provided a new strategy for experimental research on determining the optimal time for establishing CIA model and screening clinical diagnostic biomarkers.

Changes of vertical distribution of Microcystis colonies driven by short-term rainfall: Disappearance and reformation of surface bloom.

Global climate warming and human activities have increased the magnitude and frequency of Microcystis surface blooms, posing significant threats to freshwater ecosystems and human health over recent decades. Heavy rainfall events have been reported to cause the disappearance of these blooms. Although some studies have employed turbulence models to analyze the movement characteristics of Microcystis colonies, the impact of rainfall is complex, comprehensive investigations on their vertical migration induced by short-term rainfall are still necessary. Utilizing monitoring data from eutrophic ponds and controlled simulation experiments, this study examines the short-term impacts of rainfall on the vertical distribution of Microcystis in the water column. Our findings indicate that rainfall contributes to the disappearance of Microcystis blooms by reducing the quantity of small to medium-sized colonies (0-100 µm) at the surface, subsequently decreasing the overall Microcystis biomass. As rainfall intensity increases, larger colonies migrate deeper into the water column. At a rainfall threshold of 666 mm, the difference in the median volume diameter (DV50) of Microcystis colonies between the surface and bottom reaches a minimal value of 3.09%. Post-rainfall, these colonies rapidly ascend, aggregate into larger formations, and re-establish surface blooms. The greater the rainfall, the smaller the resultant Microcystis biomass, albeit with larger aggregated colony sizes. When rainfall exceeds 222 mm, the recovery rate of surface Microcystis biomass remains below 100%, decreasing to 19.48% at 666 mm of rainfall, while the median volume diameter (DV50) of the colonies increases to 139.07% of its pre-rainfall level. Furthermore, compared to pre-rainfall conditions, the photosynthetic activity of the surface Microcystis colonies was enhanced and the secretion of EPS was increased under heavy rainfall conditions. Our results identify a critical response time of 30 min for Microcystis colonies to rainfall, after which the response ceases to intensify. These insights are crucial for predicting post-rain Microcystis bloom dynamics and aiding management authorities in timely interventions.

Effects of jujube (Ziziphus jujuba mill.) fruit extracts on oxidative stress: A systematic review and meta-analysis of rodent studies.

This study aimed to evaluate the effects of jujube (Ziziphus jujuba Mill.) fruit extracts on oxidative stress levels in rodent models. Animal studies meeting the inclusion criteria were retrieved from PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, and VIP Periodical Service Platform. The Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) risk-of-bias tool was used to evaluate the risk of bias in the included studies. A meta-analysis was performed based on the guidelines provided in the Cochrane Handbook for Systematic Reviews of Interventions (CHSRI) by using Stata 17.0 software. Nineteen studies were included in the meta-analysis. Jujube fruit extracts significantly decreased the level of malonaldehyde (MDA) and increased the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Meanwhile, there was no significant improvement in the catalase (CAT) levels. In addition, there was considerable heterogeneity in the results of the meta-analysis. The results of the subgroup analysis indicated that the animal model, type of extracts, and source of target parameters may have contributed to the heterogeneity. Jujube fruit extracts are healthy and effective antioxidant dietary supplements that may be an effective adjunctive therapy for diseases in which oxidative stress is a major pathological factor. However, the overall methodological quality of the included studies was low, and additional research is warranted.

Phenotypic features, prevalence of KCNJ11-MODY in Chinese patients with early-onset diabetes and a literature review.

OBJECTIVE: Gain-of-function (GOF) variants of KCNJ11 cause neonate diabetes and maturity-onset diabetes of the young (KCNJ11-MODY), while loss-of-function (LOF) variants lead to hyperinsulinemia hypoglycemia and subsequent diabetes. Given the limited research of KCNJ11-MODY, we aimed to analyse its phenotypic features and prevalence in Chinese patients with early-onset type 2 diabetes (EOD). DESIGN, PATIENTS AND MEASUREMENTS: We performed next-generation sequencing on 679 Chinese EOD patients to screen for KCNJ11 exons variants. Bioinformatics prediction and the American College of Medical Genetics and Genomics guidelines was used to determine the pathogenicity and diagnosed KCNJ11-MODY. A literature review was conducted to investigate the phenotypic features of KCNJ11-MODY. RESULTS: We identified six predicted deleterious rare variants in six EOD patients (0.88%). They were classified as uncertain significance (variant of uncertain significance [VUS]), but more common in this EOD cohort than a general Chinese population database, however, without significant difference (53/10,588, 0.50%) (p = .268). Among 80 previously reported patients with KCNJ11-MODY, 23.8% (19/80) carried 9 (32.1%) LOF variants, who had significantly older age at diagnosis, higher birthweight and higher fasting C-peptide compared to patients with GOF variants. Many patients carrying VUS were not correctly diagnosed. CONCLUSIONS: Some rare variants of KCNJ11 might contribute to the development of Chinese EOD, although available evidence has not enough power to support them as cause of KCNJ11-MODY. The clinical features of LOF variants were different from GOF variants in KCNJ11-MODY patients. It is necessary to evaluate the pathogenicity of VUS through function experiments.

Exploring the antimicrobial activity of rare ginsenosides and the progress of their related pharmacological effects.

BACKGROUND: Panax ginseng C. A. Mey is a precious medicinal resource that could be used to treat a variety of diseases. Saponins are the most important bioactive components of, and rare ginsenosides (Rg3, Rh2, Rk1 and Rg5, etc.) refer to the chemical structure changes of primary ginsenosides through dehydration and desugarization reactions, to obtain triterpenoids that are easier to be absorbed by the human body and have higher activity. PURPOSE: At present, the research of P. ginseng. is widely focused on anticancer related aspects, and there are few studies on the antibacterial and skin protection effects of rare ginsenosides. This review summarizes the rare ginsenosides related to bacterial inhibition and skin protection and provides a new direction for P. ginseng research. METHODS: PubMed and Web of Science were searched for English-language studies on P. ginseng published between January 2002 and March 2024. Selected manuscripts were evaluated manually for additional relevant references. This review includes basic scientific articles and related studies such as prospective and retrospective cohort studies. CONCLUSION: This paper summarizes the latest research progress of several rare ginsenosides, discusses the antibacterial effect of rare ginsenosides, and finds that ginsenosides can effectively protect the skin and promote wound healing during use, so as to play an efficient antibacterial effect, and further explore the other medicinal value of ginseng. It is expected that this review will provide a wider understanding and new ideas for further research and development of P. ginseng drugs.

A CLIC1 network coordinates matrix stiffness and the Warburg effect to promote tumor growth in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) features substantial matrix stiffening and reprogrammed glucose metabolism, particularly the Warburg effect. However, the complex interplay between these traits and their impact on tumor advancement remains inadequately explored. Here, we integrated clinical, cellular, and bioinformatics approaches to explore the connection between matrix stiffness and the Warburg effect in PDAC, identifying CLIC1 as a key mediator. Elevated CLIC1 expression, induced by matrix stiffness through Wnt/ß-catenin/TCF4 signaling, signifies poorer prognostic outcomes in PDAC. Functionally, CLIC1 serves as a catalyst for glycolytic metabolism, propelling tumor proliferation. Mechanistically, CLIC1 fortifies HIF1α stability by curbing hydroxylation via reactive oxygen species (ROS). Collectively, PDAC cells elevate CLIC1 levels in a matrix-stiffness-responsive manner, bolstering the Warburg effect to drive tumor growth via ROS/HIF1α signaling. Our insights highlight opportunities for targeted therapies that concurrently address matrix properties and metabolic rewiring, with CLIC1 emerging as a promising intervention point.

Imaging findings of type I neurofibromatosis with outcome of malignant peripheral nerve sheath tumor in the right lower extremity.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder caused by mutations of the NF1 tumor suppressor gene, characterized by café-au-lait spots, neurofibromas, and Lisch nodules. Malignant peripheral nerve sheath tumor (MPNST) is an extremely rare malignancy with neural differentiation potential. The lifetime risk of developing MPNST in NF-1 patients is 8%-13%.

Poly (ß-amino esters)/Mobil Composition of Matter 41-mediated delivery of siIL-1ß alleviates deep vein thrombosis in rat hind limbs.

Introduction: Deep vein thrombosis (DVT) is a major cause of cardiovascular disease-related deaths worldwide and is considered a thrombotic inflammatory disorder. IL-1ß, as a key promoter of venous thrombus inflammation, is a potential target for DVT treatment. Constructing a nanocarrier system for intracellular delivery of siIL-1ß to silence IL-1ß may be an effective strategy for alleviating DVT. Methods: ELISA was used to detect the expression levels of IL-1ß and t-PA in the serum of DVT patients and healthy individuals. In vitro, HUVEC cells were treated with IL-1ß, and changes in VWF and t-PA expression levels were assessed. PBAE/MCM-41@siIL-1ß (PM@siIL-1ß) nano-complexes were synthesized, the characterization and biocompatibility of PM@siIL-1ß were evaluated. A rat hind limb DVT model was established, and PM@siIL-1ß was used to treat DVT rats. Morphology of the inferior vena cava, endothelial cell count, IL-1ß, vWF, and t-PA levels, as well as changes in the p38 MAPK and NF-κB pathways, were examined in the different groups. Results: IL-1ß and t-PA were highly expressed in DVT patients, and IL-1ß treatment induced a decrease in VWF levels and an increase in t-PA levels in HUVEC cells. The synthesized PM@siIL-1ß exhibited spherical shape, good stability, high encapsulation efficiency, and high drug loading capacity, with excellent biocompatibility. In the DVT model rats, the inferior vena cava was filled with blood clots, endothelial cells increased, IL-1ß and VWF levels significantly increased, while t-PA levels were significantly downregulated. Treatment with PM@siIL-1ß resulted in reduced thrombus formation, decreased endothelial cell count, and reversal of IL-1ß, VWF, and t-PA levels. Furthermore, PM@siIL-1ß treatment significantly inhibited p38 phosphorylation and upregulation of NF-κB expression in the DVT model group. Conclusion: IL-1ß can be considered a therapeutic target for suppressing DVT inflammation. The synthesized PM@siIL-1ß achieved efficient delivery and gene silencing of siIL-1ß, demonstrating good therapeutic effects on rat hind limb DVT, including anti-thrombotic and anti-inflammatory effects, potentially mediated through the p38 MAPK and NF-κB pathways.

Can Functional Micro-organisms Associated with Pumpkin Sizes Be Sought Out from the Soil?-A Comparison of Soil Microbial Community Structures in Rhizospheres between Giant- and Small-Sized Pumpkin Varieties.

To elucidate the biological mechanisms driving the growth of various pumpkin varieties to different sizes under identical management conditions while in the same field, the soil microbial community structures in the rhizospheres of giant-pumpkin (GP) and small-pumpkin (SP) varieties were analyzed. The results revealed that a significantly higher abundance of bacterial communities could be detected in the rhizospheres of the giant pumpkin varieties, such as Gemmatimonadota, norank__f__norank__o_Gaiellales, norank__f__Gemmatimonadaceae, Bryobacter, Sphingomonas, norank__f__JG30-KF-AS9, and norank__f__norank__o___Elsterales, than in those of the small-sized pumpkins. Additionally, norank_f__norank_o__Elsterale, Ellin6067, norank_f__67-14, and Chujaibacter were unique dominant soil bacteria genera in the rhizospheres of the giant pumpkins. By contrast, Arthrobacter, norank_f__Roseiflexaceae, unclassified_f__Rhizobiaceae, Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium, Nocardioides, Mycobacterium, norank_f__norank_o__Vicinamibacterales, and Burkholderia-Caballeronia-Paraburkholderia were the unique dominant soil bacterial genera in the rhizospheres of the small pumpkins. Moreover, at the fungal genus level, unclassified_c__Chytridiomycetes, Podosphaera, and Colletotrichum presented significant differences between the giant-pumpkin (GP) and small-pumpkin (SP) rhizospheres. In addition, unclassified__p__Rozellomycota, unclassified__c__Chytridiomycetes, Penicillium, and unclassified__f__Chaetomiaceae were unique dominant soil fungal genera in the rhizospheres of the giant pumpkins (GPs). By contrast, Podosphaera, Colletotrichum, unclassified__f__Plectosphaerellaceae, unclassified__o_Boletales, Scytalidium, unclassified__p__Rozellomycota, and unclassified__o_Agaricales were the unique dominant soil fungal genera in the rhizospheres of the small pumpkins (SPs). PICRUSt and FUNGuild functional prediction analyses revealed that the giant-pumpkin rhizosphere microbial community had significantly increased translation, ribosomal structure and biogenesis, nucleotide transport and metabolism, defense mechanisms, replication, recombination and repair, wood saprotroph, and undefined saprotroph levels. The above results suggest that the soil microbial compositions differed between the rhizospheres of the giant- (GP) and small-pumpkin (SP) varieties, even though the plants were grown in the same field under identical management conditions. Meanwhile, bacterial genera such as norank_f__norank_o__Elsterale, Ellin6067, norank_f__67-14, and Chujaibacter, in addition to fungal genera such as unclassified__p__Rozellomycota, unclassified__c__Chytridiomycetes, Penicillium, and unclassified__f__Chaetomiaceae, can be speculated as potential soil functional micro-organisms associated with improved pumpkin size.

Role of excessive mitochondrial fission in seawater immersion aggravated hemorrhagic shock-induced cardiac injury and the protective effect of Mdivi-1.

AIMS: Seawater immersion significantly aggravated organ dysfunction following hemorrhagic shock, leading to higher mortality rate. However, the effective treatment are still unavailable in clinic. Mitochondria were involved in the onset and development of multiple organ function disorders, whether mitochondria participate in the cardiac dysfunction following seawater immersion combined with hemorrhagic shock remains poorly understood. Hence, we investigated the role and possible mechanism of mitochondria in seawater immersion combined with hemorrhage shock-induced cardiac dysfunction were observed. RESULTS: Mitochondrial fission protein dynamin-related protein 1 (Drp1) was activated and translocated from the cytoplasm to mitochondria in the heart following seawater immersion combined with hemorrhagic shock, leading to excessive mito-chondrial fission. Excessive mitochondrial fission disrupted mitochondrial function and structure, activated mitophagy and apoptosis. At the same time, excessive mitochondrial fission resulted in disturbance of myocardial structure, hemodynamic disorders, and ultimately provoked multiple organ dysfunction and high mortality. Further studies showed that the mitochondrial division inhibitor Mdivi-1 can signifi-cantly reverse Drp1 mitochondrial translocation and inhibit mitochondrial fragmentation, reactive oxygen species (ROS) accumulation, mitophagy and apoptosis, and then protecting circulation and vital organ functions, prolonging animal survival. INNOVATION: Our findings indicate that Drp1-mediated mitochondrial fission could be a novel therapeutic targets for the treatment of seawater immersion combined with hemorrhagic shock. CONCLUSION: Drp1 mitochondrial translocation played an important role in the cardiac dysfunction after seawater immersion combined with hemorrhage shock. Drp1-mediated excessive mitochondrial fission leads to cardiac dysfunction, due to the mitochondrial structure and bioenergetics impairment.

Design of Ultra-Narrow Bandgap Polymer Acceptors for High-Sensitivity Flexible All-Polymer Short-Wavelength Infrared Photodetectors.

All-polymer photodetectors possess unique mechanical flexibility and are ideally suitable for the application in next-generation flexible, wearable short-wavelength infrared (SWIR, 1000-2700 nm) photodetectors. However, all-polymer photodetectors commonly suffer from low sensitivity, high noise, and low photoresponse speed in the SWIR region, which significantly diminish their application potential in wearable electronics. Herein, two polymer acceptors with absorption beyond 1000 nm, namely P4TOC-DCBT and P4TOC-DCBSe, were designed and synthesized. The two polymers possess rigid structure and good conformational stability, which is beneficial for reducing energetic disorder and suppressing dark current. Owing to the efficient charge generation and ultralow noise current, the P4TOC-DCBT-based all-polymer photodetector achieved a specific detectivity () of over 1012 Jones from 650 (visible) to 1070 nm (SWIR) under zero bias, with a response time of 1.36 µs. These are the best results for reported all-polymer SWIR photodetectors in photovoltaic mode. More significantly, the all-polymer blend films exhibit good mechanical durability, and hence the P4TOC-DCBT-based flexible all-polymer photodetectors show a small performance attenuation (<4%) after 2000 cycles of bending to a 3 mm radius. The all-polymer flexible SWIR organic photodetectors  are successfully applied in pulse signal detection, optical communication and image capture.

The mitochondrial division inhibitor Mdivi-1 protected organ function and extended the treatment window in rats with uncontrolled haemorrhagic shock.

AIM: To elucidate whether the application of the mitochondrial division inhibitor Mdivi-1 can protect organ function and prolong the treatment window for traumatic hemorrhagic shock. METHODS: Before definitive haemostasis treatment, Mdivi-1 (0.25 mg/kg, 0.5 mg/kg and 1 mg/kg) was administered to uncontrolled haemorrhagic shock (UHS) model rats. Lactate Ringer's solution plus hydroxyethyl starch (130/0.4) was used as a control. The effects of Mdivi-1 on blood loss, fluid demand, survival time, vital organ function, myocardial mitochondrial structure, and mitochondrial function of the heart, liver, kidney and intestine, and oxidative stress at 1 hour after hypotensive resuscitation (50-60 mmHg) were investigated. In addition, we investigated the effect of varying doses of Mdivi-1 on the maintenance time of hypotensive resuscitation without definitive haemostasis and the beneficial effect of Mdivi-1 after prolonging the duration of hypotensive resuscitation to 2 hours. RESULTS: Compared to conventional resuscitative fluid, Mdivi-1 significantly reduced blood loss and fluid demand, improved important organ functions during hypotensive resuscitation, improved animal survival and reduced the incidence of early death. Mdivi-1 significantly alleviated oxidative stress injury, reduced mitochondrial damage and restored myocardial mitochondrial structure and mitochondrial function of the heart, liver, kidney and intestine. In addition, Mdivi-1 increased the maintenance time of hypotensive resuscitation and improved rat survival after the duration of hypotensive resuscitation was prolonged to 2 h. CONCLUSIONS: Mdivi-1 significantly prolonged the treatment window for traumatic hemorrhagic shock to 2 hours in UHS model rats. The underlying mechanism may be that Mdivi-1 inhibits excessive mitochondrial fission and oxidative stress and improves the structure and function of mitochondria.

Diagnostic significance of LncRNA MIAT in periodontitis and the molecular mechanisms influencing periodontal ligament fibroblasts via the miR-204-5p/DKK1 axis.

OBJECTIVE: This study investigated the clinical importance of long noncoding RNA myocardial infarction-associated transcript (MIAT) in periodontitis and its impact on the functional regulation of human periodontal ligament fibroblasts (hPDLFs). METHODS: Ninety-eight periodontitis patients and 74 healthy controls were enrolled. In vitro cellular models were created using Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) to stimulate hPDLFs. Real-time quantitative polymerase chain reaction was used to measure mRNA levels of MIAT and osteogenic factors. Inflammation factor concentration was assessed using an enzyme-linked immunosorbent assay. Cell viability and apoptosis were examined by cell counting kit -8 and flow cytometry assay. The targeting relationship was verified by the dual-luciferase reporter and RNA Immunoprecipitation assay. RESULTS: Highly expressed MIAT and Dicckopf-1 (DDK1), and lowly expressed miR-204-5p were found in the gingival crevicular fluid of periodontitis patients and Pg-LPS induced hPDLFs. MIAT has a sensitivity of 76.53 % and a specificity of 86.49 % for identifying patients with periodontitis among healthy individuals. MIAT acts as a sponge for miR-204-5p and upregulates DDK1 mRNA expression. Silencing of MIAT diminished the promotion of apoptosis and inflammation in hPDLFs by Pg-LPS and enhanced osteogenic differentiation. However, a miR-204-5p inhibitor significantly reversed the effect of silenced MIAT. CONCLUSIONS: MIAT may act as a promising biomarker for periodontitis. It modulates apoptosis, inflammation, and osteogenic differentiation of PDLFs by focusing on the miR-204-5p/DKK1 axis, indicating its potential as a new therapeutic target for treating periodontitis.

Surgical treatment for medium-sized cystic osteochondral lesions of the talus: Autologous osteoperiosteal transplantation provides better clinical outcomes than bone marrow stimulation when cysts are deeper than 6 mm.

PURPOSE: To compare clinical outcomes of autologous osteoperiosteal transplantation versus bone marrow stimulation (BMS) for medium-sized (100-150 mm2) cystic osteochondral lesions of the talus (OLTs) and assess the correlation between patient demographics and outcomes. It was hypothesised that autologous osteoperiosteal transplantation would provide better clinical outcomes than BMS for medium-sized cystic OLTs. METHODS: Patients who underwent autologous osteoperiosteal transplantation or BMS for medium-sized cystic OLTs between 2014 and 2019 were retrospectively evaluated. According to their characteristics, a 1:1 propensity-score matching was performed and 33 pairs of patients were matched. The visual analogue scale, American Orthopaedic Foot and Ankle Society (AOFAS) score, Foot Ankle Outcome Score (FAOS) and Ankle Activity Score were collected preoperatively and at the last follow-up. In addition, a general linear model analysis was performed between patient demographics and clinical outcomes in two groups separately to detect potential risk factors. RESULTS: Finally, 28 patients in the grafted group and 27 patients in the BMS group completed the follow-up and were enrolled with a mean follow-up period of 63.5 ± 13.9 months. Both groups showed significant improvement in all patient-reported outcomes (p < 0.01). At the final follow-up, no significant differences between groups were found in all postoperative scores except FAOS Pain (p = 0.02). Correlation analysis showed a moderate correlation between cyst depth and the postoperative AOFAS score in the BMS group (r = -0.48, p = 0.01). Based on the regression line, the patients in the BMS group with a cyst deeper than 6 mm showed a lower AOFAS score than the mean score (88.7 ± 9.5) of the grafted group. CONCLUSION: Autologous osteoperiosteal transplantation and BMS are both safe and effective for medium-sized cystic OLTs. However, autologous osteoperiosteal transplantation is expected to provide better clinical outcomes than BMS when the cysts are deeper than 6 mm. LEVEL OF EVIDENCE: Level III.