Neoadjuvant tislelizumab plus stereotactic body radiotherapy and adjuvant tislelizumab in early-stage resectable hepatocellular carcinoma: the Notable-HCC phase 1b trial.

Notable-HCC (NCT05185531) is a phase 1b trial, aiming to evaluate the safety and preliminary effectiveness of neoadjuvant PD-1 blockade plus stereotactic body radiotherapy (SBRT) in early-stage resectable hepatocellular carcinoma (HCC). Twenty patients with HCC of BCLC stage 0-A received 3 × Gy SBRT and two cycles of tislelizumab, an anti-PD-1 monoclonal antibody before the curative HCC resection. Primary endpoints were the surgery delay, radiographic and pathological tumor response after the neoadjuvant therapy, safety and tolerability. During the neoadjuvant therapy, treatment-related adverse events (TRAEs) of grade 1-2 occurred in all 20 patients (100%), eight patients (40%) had grade 3 TRAEs, no grade 4 to 5 TRAE occurred, and all resolved without corticosteroids treatment. Per mRECIST, the objective response rate was 63.2% (12/19), with 3 complete response; the disease control rate was 100%. Two (10.5%) patients achieved complete pathological response. No surgery delay occurred. The neoadjuvant therapy did not increase the surgical difficulty or the incidence of complications. Secondary endpoints of disease-free survival and overall survival were not mature at the time of the analysis. Our pilot trial shows that neoadjuvant therapy with anti-PD-1 + SBRT is safe and promotes tumor responses in early-stage resectable HCC.

Tissue damage, antioxidant capacity, transcriptional and metabolic regulation of red drum Sciaenops ocellatus in response to nanoplastics exposure and subsequent recovery.

Nanoplastics are recognized as emerging contaminants that can cause severe toxicity to marine fishes. However, limited researches were focusing on the toxic effects of nanoplastics on marine fish, especially the post-exposure resilience. In this study, red drum (Sciaenops ocellatus) were exposed to 5 mg/L polystyrene nanoplastics (100 nm, PS-NPs) for a 7-day exposure experiment, and a 14-day recovery experiment that followed. The aim was to evaluate the dynamic alterations in hepatic and branchial tissue damage, hepatic antioxidant capacity, as well as hepatic transcriptional and metabolic regulation in the red drum during exposure and post-exposure to PS-NPs. Histopathological observation found that PS-NPs primarily triggered hepatic lipid droplets and branchial epithelial liftings, a phenomenon persistently discernible up to the 14 days of recovery. Although antioxidant capacity partially recovered during recovery periods, PS-NPs resulted in a sustained reduction in hepatic antioxidant activity, causing oxidative damage throughout the entire exposure and recovery phases, as evidenced by decreased total superoxide dismutase activities and increased malondialdehyde content. At the transcriptional and metabolic level, PS-NPs primarily induced lipid metabolism disorders, DNA damage, biofilm disruption, and mitochondrial dysfunction. In the gene-metabolite correlation interaction network, numerous CcO (cytochrome c oxidase) family genes and lipid metabolites were identified as key regulatory genes and metabolites in detoxification processes. Among them, the red drum possesses one additional CcO6B in comparison to human and zebrafish, which potentially contributes to its enhanced capacity for maintaining a stable and positive regulatory function in detoxification. This study revealed that nanoplastics cause severe biotoxicity to red drum, which may be detrimental to the survival of wild populations and affect the economics of farmed populations.

Beyond Small Molecules: Antibodies and Peptides for Fibroblast Activation Protein Targeting Radiopharmaceuticals.

Fibroblast activation protein (FAP) is a serine protease characterized by its high expression in cancer-associated fibroblasts (CAFs) and near absence in adult normal tissues and benign lesions. This unique expression pattern positions FAP as a prospective biomarker for targeted tumor radiodiagnosis and therapy. The advent of FAP-based radiotheranostics is anticipated to revolutionize cancer management. Among various types of FAP ligands, peptides and antibodies have shown advantages over small molecules, exemplifying prolonged tumor retention in human volunteers. Within its scope, this review summarizes the recent research progress of the FAP radiopharmaceuticals based on antibodies and peptides in tumor imaging and therapy. Additionally, it incorporates insights from recent studies, providing valuable perspectives on the clinical utility of FAP-targeted radiopharmaceuticals.

Azobenzene-based colorimetric and fluorometric chemosensor for nitroxyl releasing.

The precise release and characterization of nitroxyl (HNO) gas signaling molecule remain a challenge due to its short lifetime to date. To solve this issue, an azobenzene-based HNO donor (Azo-D1) was proposed as a colorimetric and fluorometric chemosensor for HNO releasing, to release both HNO and an azobenzene fluorescent reporter together. Specifically, the Azo-D1 has an HNO release half-life of ∼68 min under physiological conditions. The characteristic color change from the original orange to the yellow color indicated the decomposition of the donor molecule. In addition, the stoichiometry release of HNO was qualitatively and quantitatively verified through the classical phosphine compound trap. As compared with the donor molecule by itself, the decomposed product demonstrates a maximum fluorescence emission at 424 nm, where the increase of fluorescence intensity by 6.8 times can be applied to infer the real-time concentration of HNO. Moreover, cellular imaging can also be achieved using this Azo-D1 HNO donor through photoexcitation at 405 and 488 nm, where the real-time monitoring of HNO release was achieved without consuming the HNO source. Finally, the Azo-D1 HNO donor would open a new platform in the exploration of the biochemistry and the biology of HNO.

A dual-crosslinking electroactive hydrogel based on gelatin methacrylate and dibenzaldehyde-terminated telechelic polyethylene glycol for 3D bio-printing.

Gelatin was widely used as scaffold materials in 3D bio-printing due to its excellent bioactivity and availability and especially that their arginine-glycine-aspartic acid (RGD) sequences could efficiently promote cell adhesion and proliferation. In this study, an electroactive and 3D bio-printable hydrogel was prepared through a two-step chemical cross-linking process. Specifically, residual free amino groups of methacrylated gelatin (GelMA) were cross-linked with the aldehyde groups of dibenzaldehyde-terminated telechelic polyethylene glycol (DF-PEG) via Schiff base bonds, forming a gel at 37 °C. During the subsequent 3D bio-printing process, GelMA underwent UV curing, forming a secondary cross-linked network to the mechanical strength and stability of the printed structure. The uniform dispersion of carbon nanotubes (CNTs) in the GelMA/DF-PEG composite hydrogel significantly increased its conductivity. The optimized GelMA/DF-PEG composite hydrogel, i.e., 30% GelMA and 25% DF-PEG (G30D25-CNTs), exhibited superior bio-printability. When the content of CNTs was above 4%, the conductivity of G30D25-CNTs hydrogel exceeded 10-2 S/m, which satisfied the needs of cells for micro-current stimulation. Furthermore, the pore microstructures, swelling behavior, degradation ability and cell toxicity of G30D25-CNTs electroactive hydrogels were thoroughly evaluated. Thus, the G30D25-CNTs hydrogel with 4% MWCNTs could be considered for further application in electrical stimulation of tissue regeneration such as muscle and cardiac nerve tissue repair.

G-quadruplex in mitochondria as a possible biomarker for mitophagy detection.

Mitochondrial autophagy (mitophagy) is a key physiological process that maintains the homeostasis of mitochondrial quality and quantity. Monitoring mitophagy is of great significance for detecting cellular abnormalities and developing therapeutic drugs. However, there are still very few biomarkers specifically developed for monitoring mitophagy. Here, we propose for the first time that mitochondrial G-quadruplex may serve as a biomarker for mitophagy detection, and develope a fluorescent light-up probe AMTC to monitor mitophagy in live cells. During mitophagy, AMTC fluorescence is significantly enhanced, but once mitophagy is inhibited, its fluorescence immediately decreases. The fluorescence behavior of AMTC implicates an increase in the formation of mitochondrial G-quadruplex during mitophagy. This inference has also been supported by the other two G-quadruplex probes. Taken together, this work provides a new possible biomarker and detection tool for the study of mitophagy.

Electroacupuncture Mediates Fat Metabolism and Autophagy via a Sirt3-Dependent Mechanism in Mice Fed High-Fat Diet.

This study investigates the therapeutic potential of electroacupuncture (EA) on obesity, focusing on its influence on autophagy and energy metabolism, utilizing a high-fat diet (HFD)-induced mouse model. Treatment with EA significantly reduces body weight, fat deposition, and lipid accumulation in HFD-fed mice. Additionally, EA effectively ameliorates metabolic imbalances, reducing blood glucose levels and plasma markers of liver function. At the molecular level, EA enhances the expression of thermogenesis-associated genes in brown adipose tissue and decreases p53 expression, suggesting a decrease in apoptosis. Autophagy in white adipose tissue is inhibited by EA, as demonstrated by the suppression of key autophagy-related proteins. Further experiments highlight the critical role of Sirtuin 3 (Sirt3) in EA's anti-obesity effects. Sirt3 supplementation combined with EA results in reduced body weight, fat deposition, and lipid accumulation, along with modulations in key metabolic indicators. Moreover, EA's modulatory effect on uncoupling protein 1 (Ucp1), Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc-1α), and p53 is found to be Sirt3 dependent. In conclusion, EA exerts beneficial effects against obesity through Sirt3-dependent modulation of autophagy and energy metabolism, indicating a potential therapeutic approach for obesity and related metabolic disorders.

Intelligent fault diagnosis algorithm of rolling bearing based on optimization algorithm fusion convolutional neural network.

As an essential component of mechanical equipment, the fault diagnosis of rolling bearings may not only guarantee the systematic operation of the equipment, but also minimize any financial losses caused by equipment shutdowns. Fault diagnosis algorithms based on convolutional neural networks (CNN) have been widely used. However, traditional CNNs have limited feature representation capabilities, thereby making it challenging to determine their hyperparameters. This paper proposes a fault diagnosis method that combines a 1D-CNN with an attention mechanism and hyperparameter optimization to overcome the aforementioned limitations; this method improves the search speed for optimal hyperparameters of CNN models, improves the diagnostic accuracy, and enhances the representation of fault feature information in CNNs. First, the 1D-CNN is improved by combining it with an attention mechanism to enhance the fault feature information. Second, a swarm intelligence algorithm based on Differential Evolution (DE) and Grey Wolf Optimization (GWO) is proposed, which not only improves the convergence accuracy, but also increases the search efficiency. Finally, the improved 1D-CNN alongside hyperparameters optimization are used to diagnose the faults of rolling bearings. By using the Case Western Reserve University (CWRU) and Jiangnan University (JNU) datasets, when compared to other common diagnosis models, the results demonstrate the usefulness and dependability of the DE-GWO-CNN algorithm in fault diagnosis applications by demonstrating the increased diagnostic accuracy and superior anti-noise capabilities of the proposed method. The fault diagnosis methodology presented in this paper can accurately identify faults and provide dependable fault classification, thereby assisting technicians in promptly resolving faults and minimizing equipment failures and operational instabilities.

Marriage of radiotracers and total-body PET/CT rapid imaging system: current status and clinical advances.

Radiotracers and medical imaging equipment are the two main keys to molecular imaging. While radiotracers are of great interest to research and industry, medical imaging equipment technology is blossoming everywhere. Total-body PET/CT (TB-PET/CT) has emerged in response to this trend and is rapidly gaining traction in the fields of clinical oncology, cardiovascular medicine, inflammatory/infectious diseases, and pediatric diseases. In addition, the use of a growing number of radiopharmaceuticals in TB-PET/CT systems has shown promising results. Notably, the distinctive features of TB-PET/CT, such as its ultra-long axial field of view (194 cm), ultra-high sensitivity, and capability for low-dose tracer imaging, have enabled enhanced imaging quality while reducing the radiation dose. The envisioned whole-body dynamic imaging, delayed imaging, personalized disease management, and ultrafast acquisition for motion correction, among others, are achieved. This review highlights two key factors affecting molecular imaging, describing the rapid imaging effects of radiotracers allowed at low doses on TB-PET/CT and the improvements offered compared to conventional PET/CT.

Heavy Metals in Surface Sediment of Plateau Lakes in Tibet, China: Occurrence, Risk Assessment, and Potential Sources.

Tibetan Plateau lakes have high ecological value and play a crucial role in maintaining ecological balance. This research aimed to study the pollution characteristics, ecological risk, and potential sources of eight heavy metals (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) in the surface sediments of 12 Tibetan Plateau lakes. The results of the toxicity risk index (TRI) showed that only Gongzhu Tso (28.09) and La' ang Tso (20.25) had heavy metals that could pose a very high risk of toxicity to aquatic organisms. Hg posed the highest potential ecological risk to aquatic organisms. Based on the results of multiple analyses, we inferred that the contents of Cr, Cu, Hg, and Ni in sediments of Tibetan lakes were influenced by industrial and agricultural development; Cd, Pb, and Zn were influenced by transport and atmospheric transport; and As was derived from geothermal activity and rock weathering.

Mechanisms of polydatin against spinal cord ischemia-reperfusion injury based on network pharmacology, molecular docking and molecular dynamics simulation.

BACKGROUND: Polydatin has shown considerable pharmacological activities in ischemia-reperfusion injuries of various organs. However, its effects and mechanisms in spinal cord ischemia-reperfusion injury have not been fully established. In this study, the mechanisms of polydatin against spinal cord ischemia-reperfusion injury were investigated via network pharmacology, molecular docking and molecular dynamics simulation. METHODS: Spinal cord ischemia-reperfusion injury-related targets were obtained from the GeneCards database, while polydatin-related action targets were obtained from the CTD and SwissTarget databases. A protein-protein interaction network of potential targets was constructed using the String platform. After selecting the potential key targets, GO functional enrichment and KEGG pathway enrichment analyses were performed via the Metascape database, and a network map of "drug-target-pathway-disease" constructed. The relationships between polydatin and various key targets were assessed via molecular docking. Molecular dynamics simulation was conducted for optimal core protein-compound complexes obtained by molecular docking. RESULTS: Topological analysis of the PPI network revealed 14 core targets. GO functional enrichment analysis revealed that 435 biological processes, 12 cell components and 29 molecular functions were enriched while KEGG pathway enrichment analysis revealed 91 enriched signaling pathways. Molecular docking showed that polydatin had the highest binding affinity for MAPK3, suggesting that MAPK3 is a key target of polydatin against spinal cord ischemia-reperfusion injury. Molecular dynamics simulations revealed good binding abilities between polydatin and MAPK3. CONCLUSIONS: Polydatin exerts its effects on spinal cord ischemia-reperfusion injury through multiple targets and pathways. MAPK3 may be a key target of polydatin in spinal cord ischemia-reperfusion injury.

Human umbilical cord mesenchymal stem cells-derived exosomes exert anti-inflammatory effects on osteoarthritis chondrocytes.

Inflammation of chondrocytes plays a critical role in the occurrence and development of osteoarthritis (OA). Recent evidence indicated exosomes derived from mesenchymal stem cells (MSCs-Exos) exhibit excellent anti-inflammatory ability in many troublesome inflammatory diseases including OA. In the present study, we aimed to explore the role of human umbilical cord-derived MSCs-Exos (hUC-MSCs-Exos) in treating the inflammation of chondrocytes and its related mechanisms. Ultracentrifugation was applied to isolate hUC-MSCs-Exos from the culture supernatant of hUC-MSCs. Two OA-like in vitro inflammation models of human articular chondrocytes induced with interleukin 1ß (IL-1ß) and co-incubation with macrophage utilizing transwell cell culture inserts were both used to evaluate the anti-inflammatory effects of hUC-MSCs-Exos. The mRNA sequencing of chondrocytes after treatment and microRNA (miRNA) sequencing of hUC-MSCs-Exos were detected and analyzed for possible mechanism analysis. The results of the study confirmed that hUC-MSCs-Exos had a reversed effect of IL-1ß on chondrocytes in the expression of collagen type II alpha 1 (COL2A1) and matrix metalloproteinase 13 (MMP13). The addition of hUC-MSCs-Exos to M1 macrophages in the upper chamber showed down-regulation of IL-1ß and tumor necrosis factor α (TNF-α), up-regulation of IL-10 and arginase1 (ARG1), and reversed the gene and protein expression of COL2A1 and MMP13 of the chondrocytes seeded in the lower chamber. The results of this study confirmed the anti-inflammatory effects of hUC-MSCs-Exos in the human articular chondrocytes inflammation model. hUC-MSCs-Exos may be used as a potential cell-free treatment strategy for chondrocyte inflammation in OA.

Differential expression analysis of miRNAs in macrophage-derived exosomes in the tuberculosis-infected bone microenvironment.

Background: Macrophages play an important role in regulating the course of spinal tuberculosis within the bone microenvironment. This study aimed to investigate the differential expression of miRNA in macrophage-derived exosomes within the tuberculosis-infected bone microenvironment, to identify miRNAs that hold potential as diagnostic markers and therapeutic targets. Methods: We established study cohorts for spinal tuberculosis, collected bone marrow blood samples, isolated macrophage exosomes, and performed exosome miRNA sequencing. A miRNA-mRNA co-expression network was constructed using WGCNA analysis. Gene GO analysis and KEGG pathway enrichment analysis were performed using KOBAS software. Target miRNAs were selected based on fold change, P-value, and false discovery rate, and their validation was carried out using qRT-PCR and ROC curve studies. Subsequently, we constructed a target gene network for these miRNAs and performed KEGG pathway enrichment analysis to explore the potential signaling mechanisms involved in regulating the disease course of spinal tuberculosis. Results: Our findings revealed that macrophages from the tuberculosis-infected bone microenvironment exhibited an M1 phenotype. The successful extraction of exosomes from macrophage supernatants was confirmed through electron microscopy, particle size analysis, and protein blot analysis. Exosome miRNA-seq demonstrated that 28 miRNAs were up-regulated, while 34 miRNAs were down-regulated in individuals with spinal tuberculosis. GO analysis and KEGG pathway enrichment analysis indicated that the differentially expressed miRNAs were involved in various biological processes, cell components, molecular functions, and signaling pathways, which collectively contribute to the regulation of the disease course of spinal tuberculosis. Notably, miRNA-125b-5p was successfully selected based on fold change, p-value, and false discovery rate. qRT-PCR validation further confirmed the significant up-regulation of miRNA-125b-5p in spinal tuberculosis. The ROC curve revealed that miR-125b-5p is a potential diagnostic biomarker for spinal tuberculosis. Moreover, construction of the miRNA-125b-5p target gene network and subsequent KEGG enrichment analysis highlighted the importance of MAPK, TNF, Ras, Rap1, and the PI3K-Akt signaling pathways in the regulation of the disease course of spinal tuberculosis. Conclusion: Our study demonstrates differential expression of miRNAs in macrophage-derived exosomes in the tuberculosis-infected bone microenvironment. Specifically, MiRNA-125b-5p is significantly up-regulated in spinal tuberculosis and shows potential as a diagnostic biomarker for spinal tuberculosis.

Three-dimensional simulation/printing-assisted surgery for symptomatic metastatic epidural spinal cord compression of posterior column: efficacy assessment based on 2-year follow-up.

Background: Surgical intervention is necessary for resolving the symptoms of the spinal cord and nerve compression caused by symptomatic metastatic epidural spinal cord compression. However, surgeons are constantly seeking ways to improve surgical efficiency and safety. This study aims to evaluate the efficacy of 3D simulation/printing-assisted surgery for symptomatic metastatic epidural spinal cord compression of the posterior column. Methods: We retrospectively analyzed the clinical data of patients who underwent surgical treatment for symptomatic metastatic epidural spinal cord compression of the posterior column in our hospital from January 2015 to January 2020. The simulated group underwent a 3D digital simulation of the lesion area using imaging data before surgery. Twelve patients in the simulated group also received 3D printing, while the direct surgery group did not receive any 3D simulation or printing. All patients were followed up for at least 2 years. We collected clinical data, including operation time, intraoperative blood loss, pedicle screw adjustment rate, intraoperative fluoroscopy times, the incidence of dural injury and cerebrospinal fluid leakage, VAS score, postoperative neurological function improvement, and tumor recurrence. Statistical analysis was performed using SPSS23.0, and P < 0.05 was considered statistically significant. Results: A total of 46 patients were included in this study, with 20 in the simulated group and 26 in the non-simulated group. The simulated group had better operation time, intraoperative blood loss, screw adjustment rate, fluoroscopy times, and incidence of dural injury/cerebrospinal fluid leakage compared to the non-simulated group. The VAS scores of the two groups improved significantly after the operation and at the last follow-up compared to before the operation. However, there was no statistically significant difference between the two groups. There was also no statistically significant difference in neurological function improvement between the two groups. In the simulated group, 25% of patients relapsed, while in the non-simulated group, 34.61% of patients relapsed. However, there was no statistical difference between the two groups. Conclusion: Preoperative 3D simulation/printing-assisted surgery is a practical and feasible approach for treating symptomatic metastatic epidural spinal cord compression of the posterior column.

Real-world practice of conversion surgery for unresectable hepatocellular carcinoma - a single center data of 26 consecutive patients.

AIM: To understand the proportion of uHCC (unresectable hepatocellular carcinoma) patients who achieve successful conversion resection in a high-volume setting with state of the art treatment options. METHODS: We retrospectively reviewed all HCC patients hospitalized to our center from June 1st, 2019 to June 1st, 2022. Conversion rate, clinicopathological features, response to systemic and/or loco-regional therapy and surgical outcomes were analyzed. RESULTS: A total of 1,904 HCC patients were identified, with 1672 patients receiving anti-HCC treatment. 328 patients were considered up-front resectable. Of the remaining 1344 uHCC patients, 311 received loco-regional treatment, 224 received systemic treatment, and the remainder (809) received combination systemic plus loco-regional treatment. Following treatment, one patient from the systemic group and 25 patients from the combination group were considered to have resectable disease. A high objective response rate (ORR) was observed in these converted patients (42.3% under RECIST v1.1 and 76.9% under mRECIST criteria). The disease control rate (DCR) reached 100%. 23 patients underwent curative hepatectomy. Major post-operative morbidity was equivalent in the both groups (P=0.76). Pathologic complete response (pCR) was 39.1%. During conversion treatment, grade 3 or higher treatment-related adverse events (TRAEs) were observed in 50% of patients. The median follow-up time was 12.9 months (range, 3.9~40.6) from index diagnosis and 11.4 months (range, 0.9~26.9) from resection. Three patients experienced disease recurrence following conversion surgery. CONCLUSIONS: By intensive treatment, a small sub-group of uHCC patients (2%) may potentially be converted to curative resection. Loco-regional combined with systemic modality was relative safe and effective in the conversion therapy. Short-term outcomes are encouraging, but long-term follow-up in a larger patient population are required to fully understand the utility of this approach.

AHY-SLAM: Toward Faster and More Accurate Visual SLAM in Dynamic Scenes Using Homogenized Feature Extraction and Object Detection Method.

At present, SLAM is widely used in all kinds of dynamic scenes. It is difficult to distinguish dynamic targets in scenes using traditional visual SLAM. In the matching process, dynamic points are incorrectly added to the pose calculation with the camera, resulting in low precision and poor robustness in the pose estimation. This paper proposes a new dynamic scene visual SLAM algorithm based on adaptive threshold homogenized feature extraction and YOLOv5 object detection, named AHY-SLAM. This new method adds three new modules based on ORB-SLAM2: a keyframe selection module, a threshold calculation module, and an object detection module. The optical flow method is used to screen keyframes for each frame input in AHY-SLAM. An adaptive threshold is used to extract feature points for keyframes, and dynamic points are eliminated with YOLOv5. Compared with ORB-SLAM2, AHY-SLAM has significantly improved pose estimation accuracy over multiple dynamic scene sequences in the TUM open dataset, and the absolute pose estimation accuracy can be increased by up to 97%. Compared with other dynamic scene SLAM algorithms, the speed of AHY-SLAM is also significantly improved under a guarantee of acceptable accuracy.

Synthesis and nitroxyl (HNO) donating properties of benzoxadiazole-based Piloty's acids.

Developing functional nitroxyl (HNO) donors play a significant role in the further exploration of endogenous HNO in biochemistry and pharmacology. In this work, two novel Piloty's acids (SBD-D1 and SBD-D2) were proposed by incorporating benzoxadiazole-based fluorophores, in order to achieve the dual-function of releasing both HNO and a fluorophore in situ. Under physiological conditions, both SBD-D1 and SBD-D2 efficiently donated HNO (t1/2 = 10.96 and 8.18 min, respectively). The stoichiometric generation of HNO was determined by both Vitamin B12 and phosphine compound trap. Interestingly, due to the different substitution groups on the aromatic ring, SBD-D1 with the chlorine showed no fluorescence emission, but SBD-D2 was strongly fluorescent due to the presence of the dimethylamine group. Specifically, the fluorescent signal would decrease during the release process of HNO. Moreover, theoretical calculations were performed to understand the emission difference. A strong radiation derived from benzoxadiazole with dimethylamine group due to the large transition dipole moment (∼4.3 Debye), while the presence of intramolecular charge transfer process in the donor with chlorine group caused a small transition dipole moment (<0.1 Debye). Finally, these studies would contribute to the future design and application of novel functional HNO donors for the exploration of HNO biochemistry and pharmacology.

Protective effects of polydatin against bone and joint disorders: the in vitro and in vivo evidence so far.

Polydatin is an active polyphenol displaying multifaceted benefits. Recently, growing studies have noticed its potential therapeutic effects on bone and joint disorders (BJDs). Therefore, this article reviews recent in vivo and in vitro progress on the protective role of polydatin against BJDs. An insight into the underlying mechanisms is also presented. It was found that polydatin could promote osteogenesis in vitro, and symptom improvements have been disclosed with animal models of osteoporosis, osteosarcoma, osteoarthritis and rheumatic arthritis. These beneficial effects obtained in laboratory could be mainly attributed to the bone metabolism-regulating, anti-inflammatory, antioxidative, apoptosis-regulating and autophagy-regulating functions of polydatin. However, studies on human subjects with BJDs that can lead to early identification of the clinical efficacy and adverse effects of polydatin have not been reported yet. Accordingly, this review serves as a starting point for pursuing clinical trials. Additionally, future emphasis should also be devoted to the low bioavailability and prompt metabolism nature of polydatin. In summary, well-designed clinical trials of polydatin in patients with BJD are in demand, and its pharmacokinetic nature must be taken into account.

Gut microbial community structure and function of Przewalski's horses varied across reintroduced sites in China.

Host-associated microbiota can significantly impact host fitness. Therefore, naturally occurring variations in microbiota may influence the health and persistence of their hosts. This finding is particularly important in reintroduced animals, as they typically experience habitat changes during translocations. However, little is known about how microbiomes are altered in response to conservation translocation. Here, we accessed the gut microbiome of Przewalski's horse (Equus przewalskii) populations in China from three nature reserves (i.e. Xinjiang Kalamaili Nature Reserve, KNR; Dunhuang Xihu National Nature Reserve, DXNNR; and Anxi Extreme-arid Desert Nature Reserve, AENR) using 16s rRNA gene and metagenome sequencing. The results showed that the microbial composition and function differed significantly across locations, while a subset of core taxa was consistently present in most of the samples. The abundance of genes encoding microbe-produced enzymes involved in the metabolism of carbohydrates, especially for glycoside hydrolases, was significantly higher in open-spaced KNR populations than in more confined AENR individuals. This study offers detailed and significant differential characters related to the microbial community and metabolic pathways in various reintroduced sites of Przewalski's horse, which might provide a basis for future microecological and conservation research on endangered reintroduced animals.