In vitro simulated saliva, gastric, and intestinal digestion followed by faecal fermentation reveals a potential modulatory activity of Epimedium on human gut microbiota.

Herba Epimedii, known for its rich array of bioactive ingredients and widespread use in ethnopharmacological practices, still lacks a comprehensive understanding of its gastrointestinal biotransformation. In this study, we qualitatively explored the dynamic changes in Epimedium sagittatum components during in vitro simulated digestions, with a quantitative focus on its five major flavonoids. Notably, significant metabolism of E. sagittatum constituents occurred in the simulated small intestinal fluid and colonic fermentation stages, yielding various low molecular weight metabolites. Flavonoids like kaempferol glycosides were fully metabolized in the simulated intestinal fluid, while hyperoside digestion occurred during simulated colon digestion. Colonic fermentation led to the production of two known bioactive isoflavones, genistein, and daidzein. The content and bioaccessibility of the five major epimedium flavonoids-icariin, epimedin A, epimedin B, epimedin C, and baohuoside I-significantly increased after intestinal digestion. During colon fermentation, these components gradually decreased but remained incompletely metabolized after 72 h. Faecal samples after E. sagittatum fermentation exhibited shift towards dominance by Lactobacillus (Firmicutes), Bifidobacterium (Actinobacteria), Streptococcus (Firmicutes), and Dialister (Firmicutes). These findings enhance our comprehension of diverse stages of Herba Epimedii constituents in the gut, suggesting that the primary constituents become bioaccessible in the colon, where new bioactive compounds may emerge.

Dehydrozaluzanin C- derivative protects septic mice by alleviating over-activated inflammatory response and promoting the phagocytosis of macrophages.

Host-directed therapy (HDT) is a new adjuvant strategy that interfere with host cell factors that are required by a pathogen for replication or persistence. In this study, we assessed the effect of dehydrozaluzanin C-derivative (DHZD), a modified compound from dehydrozaluzanin C (DHZC), as a potential HDT agent for severe infection. LPS-induced septic mouse model and Carbapenem resistant Klebsiella pneumoniae (CRKP) infection mouse model was used for testing in vivo. RAW264.7 cells, mouse primary macrophages, and DCs were used for in vitro experiments. Dexamethasone (DXM) was used as a positive control agent. DHZD ameliorated tissue damage (lung, kidney, and liver) and excessive inflammatory response induced by LPS or CRKP infection in mice. Also, DHZD improved the hypothermic symptoms of acute peritonitis induced by CRKP, inhibited heat-killed CRKP (HK-CRKP)-induced inflammatory response in macrophages, and upregulated the proportions of phagocytic cell types in lungs. In vitro data suggested that DHZD decreases LPS-stimulated expression of IL-6, TNF-α and MCP-1 via PI3K/Akt/p70S6K signaling pathway in macrophages. Interestingly, the combined treatment group of DXM and DHZD had a higher survival rate and lower level of IL-6 than those of the DXM-treated group; the combination of DHZD and DXM played a synergistic role in decreasing IL-6 secretion in sera. Moreover, the phagocytic receptor CD36 was increased by DHZD in macrophages, which was accompanied by increased bacterial phagocytosis in a clathrin- and actin-dependent manner. This data suggests that DHZD may be a potential drug candidate for treating bacterial infections.

Multi-modal molecular determinants of clinically relevant osteoporosis subtypes.

Due to a rapidly aging global population, osteoporosis and the associated risk of bone fractures have become a wide-spread public health problem. However, osteoporosis is very heterogeneous, and the existing standard diagnostic measure is not sufficient to accurately identify all patients at risk of osteoporotic fractures and to guide therapy. Here, we constructed the first prospective multi-omics atlas of the largest osteoporosis cohort to date (longitudinal data from 366 participants at three time points), and also implemented an explainable data-intensive analysis framework (DLSF: Deep Latent Space Fusion) for an omnigenic model based on a multi-modal approach that can capture the multi-modal molecular signatures (M3S) as explicit functional representations of hidden genotypes. Accordingly, through DLSF, we identified two subtypes of the osteoporosis population in Chinese individuals with corresponding molecular phenotypes, i.e., clinical intervention relevant subtypes (CISs), in which bone mineral density benefits response to calcium supplements in 2-year follow-up samples. Many snpGenes associated with these molecular phenotypes reveal diverse candidate biological mechanisms underlying osteoporosis, with xQTL preferences of osteoporosis and its subtypes indicating an omnigenic effect on different biological domains. Finally, these two subtypes were found to have different relevance to prior fracture and different fracture risk according to 4-year follow-up data. Thus, in clinical application, M3S could help us further develop improved diagnostic and treatment strategies for osteoporosis and identify a new composite index for fracture prediction, which were remarkably validated in an independent cohort (166 participants).

Comparative research on the pipe-soil frictional resistances of circular and rectangular pipe sections during trenchless pipe jacking.

Pipe jacking is a trenchless construction method to achieve forward tunneling and efficient construction of underground structure simultaneously without extensive surface excavation. In the process of pipe jacking construction, the jacking force provided by the hydraulic jacking equipment must overcome the frontal resistance of the cutter head and the frictional resistance between the pipe sections and formation at the same time. In particular, the pipe-soil frictional resistance increases with the increases of jacking distance, buried depth, pipe diameter and the complexity of jacking trajectory. Therefore, it is very important to correctly estimate jacking force in trenchless jacking engineering practice for the smooth implementation of pipe jacking, operation risk and comprehensive cost control. Firstly, the stress states of jacking circular and rectangular pipe sections in the soil are analyzed, and the key influencing factors of their pipe-soil frictional resistance are obtained respectively. Then, the pipe-soil frictional resistance of jacking the circular and rectangular pipe sections with the same external surface area in the dry sandy soil and coal granular layer are tested separately by using the self-developed multifunctional experimental apparatus during trenchless pipe jacking. The results show that the pipe-soil frictional resistances of jacking circular and rectangular pipe sections in the coal granular layer are always smaller than that in the sandy soil under the same experimental conditions, and the corresponding fitting calculation equation of pipe-soil frictional resistances are obtained respectively. Meanwhile, the modified calculation methods of the above pipe-soil frictional resistances are proposed respectively based on the relationship between the lateral pressure coefficient K and the buried depth of pipe section H. Moreover, the disturbed area of soil in the upper part of jacking circular pipe section presents an arc distribution, while the disturbed area of soil in the upper part of jacking rectangular pipe section presents a slightly concave distribution. Due to the different disturbance conditions of soil around the pipe section, the lateral pressure coefficient K should be corrected in the calculation equations of pipe-soil frictional resistance of jacking circular and rectangular pipe sections based on the discrete element numerical simulation analysis by EDEM software. Finally, the pipe-soil frictional resistances obtained by different methods in the sandy soil are compared and analyzed. The calculated values of the modified theoretical calculation method are very close to the experimental test values, while the other methods are smaller than the experimental test values, which makes the rationality of the modified theoretical calculation method of pipe-soil frictional resistance is verified, and some suggestions are also put forward for the value of some coefficients in the relevant empirical estimation equations. The above research achievements systematically compared the states of pipe-soil frictional resistances of jacking circular and rectangular pipe sections based on different research methods, especially for the correct evaluation of jacking force during trenchless pipe jacking, they could provide some valuable references and effective guidance for the subsequent research, engineering practice and further development of trenchless pipe jacking technology.

Charge-Assisted Ionic Hydrogen-Bonded Organic Frameworks: Designable and Stabilized Multifunctional Materials.

Hydrogen-bonded organic frameworks (HOFs) are a class of crystalline framework materials assembled by hydrogen bonds. HOFs have the advantages of high crystallinity, mild reaction conditions, good solution processability, and reproducibility. Coupled with the reversibility and flexibility of hydrogen bonds, HOFs can be assembled into a wide diversity of crystalline structures. Since the bonding energy of hydrogen bonds is lower than that of ligand and covalent bonds, the framework of HOFs is prone to collapse after desolventisation and the stability is not high, which limits the development and application of HOFs. In recent years, numerous stable and functional HOFs have been developed by π-π stacking, highly interpenetrated networks, charge-assisted, ligand-bond-assisted, molecular weaving, and covalent cross-linking. Charge-assisted ionic HOFs introduce electrostatic attraction into HOFs to improve stability while enriching structural diversity and functionality. In this paper, we review the development, the principles of rational design and assembly of charge-assisted ionic HOFs, and introduces the different building block construction modes of charge-assisted ionic HOFs. Highlight the applications of charge-assisted ionic HOFs in gas adsorption and separation, proton conduction, biological applications, etc., and prospects for the diverse design of charge-assisted ionic HOFs structures and multifunctional applications.

Radiomics using CT images for preoperative prediction of lymph node metastasis in perihilar cholangiocarcinoma: a multi-centric study.

OBJECTIVES: To develop a CT-based radiomics model for preoperative prediction of lymph node (LN) metastasis in perihilar cholangiocarcinoma (pCCA). METHODS: The study enrolled consecutive pCCA patients from three independent Chinese medical centers. The Boruta algorithm was applied to build the radiomics signature for the primary tumor and LN. The k-means algorithm was employed to cluster the selected LNs based on the radiomics signature LN. Support vector machines were used to construct the prediction models. The diagnostic efficiency was measured by the area under the receiver operating characteristic curve (AUC). The optimal model was evaluated in terms of calibration, clinical usefulness, and prognostic value. RESULTS: A total of 214 patients were included in the study (mean age: 61.6 years ± 9.4; 130 male). The selected LNs were classified into two clusters, which were significantly correlated with LN metastasis in all cohorts (p < 0.001). The model incorporated the clinical risk factors, radiomics signature primary tumor, and the LN cluster obtained the best discrimination, with AUC values of 0.981 (95% CI: 0.962-1), 0.896 (95% CI: 0.810-0.982), and 0.865 (95% CI: 0.768-0.961) in the training, internal validation, and external validation cohorts, respectively. High-risk patients predicted by the optimal model had shorter overall survival than low-risk patients (median, 13.7 vs. 27.3 months, p < 0.001). CONCLUSIONS: The study proposed a radiomics model with good performance to predict LN metastasis in pCCA. As a noninvasive preoperative prediction tool, this model may help in patient risk stratification and personalized treatment. CLINICAL RELEVANCE STATEMENT: A CT-based radiomics model accurately predicts lymph node metastasis in perihilar cholangiocarcinoma patients. This noninvasive preoperative tool can aid in patient risk stratification and personalized treatment, potentially improving patient outcomes. KEY POINTS: • The radiomics model based on contrast-enhanced CT is a useful tool for preoperative prediction of lymph node metastasis in perihilar cholangiocarcinoma. • Radiomics features extracted from lymph nodes show great potential for predicting lymph node metastasis. • The study is the first to identify a lymph node phenotype with a high probability of metastasis based on radiomics.

In Situ Forming Gel Polymer Electrolyte for High Energy-Density Lithium Metal Batteries.

In situ forming gel polymer electrolyte (GPE) is one of the most feasible ways to improve the safety and cycle performances of lithium metal batteries with high energy density. However, most of the in situ formed GPEs are not compatible with high-voltage cathode materials. Here, this work provides a novel strategy to in situ form GPE based on the mechanism of Ritter reaction. The Ritter reaction in liquid electrolyte has the advantage of appropriate reaction temperature and no additional additives. The polymer chains are cross-linked by amide groups with the formation of GPE with superior electrochemical properties. The GPE has high ionic conductivity (1.84 mS cm-1 ), wide electrochemical stability window (>5.25 V) and high lithium ion transference number (≈0.78), compatible with high-voltage cathode materials. The Li|LiNi0.6 Co0.2 Mn0.2 O2 batteries with in situ formed GPE show excellent long-term cycle stability (93.4%, 300 cycles). The density functional theory calculation and X-ray photoelectron spectroscopy results verify that the amide and nitrile groups are beneficial for stabilizing cathode structure and promoting uniform Li deposition on Li anode. Furthermore, the in situ formed GPE exhibits excellent electrochemical performance in Graphite|LiMn2 O4 and Graphite|LiNi0.5 Co0.2 Mn0.3 O2 pouch batteries. This approach is adaptable to current battery technologies, which will be sure to promote the development of high energy-density lithium-ion batteries.

Prognostic impact and immunotherapeutic implications of NETosis-related gene signature in gastric cancer patients.

The role of NETosis and its related molecules remains unclear in gastric cancer. The data used in this study was directly downloaded from the Cancer Genome Atlas (TCGA) database. All analysis and plots are completed in R software using diverse R packages. In our study, we collected the list of NETosis-related genes from previous publications. Based on the list and expression profile of gastric cancer patients from the TCGA database, we identified the NETosis-related genes significantly correlated with patients survival. Then, CLEC6A, BST1 and TLR7 were identified through LASSO regression and multivariate Cox regression analysis for prognosis model construction. This prognosis model showed great predictive efficiency in both training and validation cohorts. We noticed that the high-risk patients might have a worse survival performance. Next, we explored the biological enrichment difference between high- and low-risk patients and found that many carcinogenic pathways were upregulated in the high-risk patients. Meanwhile, we investigated the genomic instability, mutation burden and immune microenvironment difference between high- and low-risk patients. Moreover, we noticed that low-risk patients were more sensitive to immunotherapy (85.95% vs. 56.22%). High-risk patients were more sensitive to some small molecules compounds like camptothecin_1003, cisplatin_1005, cytarabine_1006, nutlin-3a (-)_1047, gemcitabine_1190, WZ4003_1614, selumetinib_1736 and mitoxantrone_1810. In summary, our study comprehensively explored the role of NETosis-related genes in gastric cancer, which can provide direction for relevant studies.

Photomultiplication Behavior of Chlorophyll-Based Photodetector under Biased Voltage.

In this study, we fabricated a photodetector (PD) with two types of chlorophyll derivatives, namely, zinc methyl 3-devinyl-3-hydroxymethyl-pyropheophorbide-a (ZnChl) and methyl 131-deoxo-131-dicyanomethylene-pyropheophorbide-a (H2Chl'), via a two-step drop-coating process. In the absorption range of ZnChl/H2Chl' films, the maximum external quantum efficiency of ZnChl/H2Chl'-based devices reached 1363% at -8 V and 1345% at 2.5 V, exhibiting the photomultiplication (PM) phenomenon. The PM phenomenon of ZnChl/H2Chl'-based devices is attributed to hole tunneling injection from the external circuit assisted by electron accumulation in the ZnChl and H2Chl' under light illumination. Through the investigation of the responsivity (R) of ZnChl/H2Chl'-based devices, it has been found that achieving a high R is easier under forward bias compared with reverse bias (7706 mA/W at -8 V and 7629 mA/W at 2.5 V). The organic PDs based on ZnChl/H2Chl' exhibit PM behavior, offering a promising approach to improve the device's responsivity.

Collaborative Camouflaged Object Detection: A Large-Scale Dataset and Benchmark.

In this article, we provide a comprehensive study of a new task called collaborative camouflaged object detection (CoCOD), which aims to simultaneously detect camouflaged objects with the same properties from a group of relevant images. To this end, we meticulously construct the first large-scale dataset, termed CoCOD8K, which consists of 8528 high-quality and elaborately selected images with object mask annotations, covering five superclasses and 70 subclasses. The dataset spans a wide range of natural and artificial camouflage scenes with diverse object appearances and backgrounds, making it a very challenging dataset for CoCOD. Besides, we propose the first baseline model for CoCOD, named bilateral-branch network (BBNet), which explores and aggregates co-camouflaged cues within a single image and between images within a group, respectively, for accurate camouflaged object detection (COD) in given images. This is implemented by an interimage collaborative feature exploration (CFE) module, an intraimage object feature search (OFS) module, and a local-global refinement (LGR) module. We benchmark 18 state-of-the-art (SOTA) models, including 12 COD algorithms and six CoSOD algorithms, on the proposed CoCOD8K dataset under five widely used evaluation metrics. Extensive experiments demonstrate the effectiveness of the proposed method and the significantly superior performance compared to other competitors. We hope that our proposed dataset and model will boost growth in the COD community. The dataset, model, and results will be available at: https://github.com/zc199823/BBNet-CoCOD.

Pathogenesis of myopic choroidal neovascularization: A systematic review and meta-analysis.

Myopic choroidal neovascularization (CNV) is a vision-threatening complication of high myopia. Here, we systematically review cohort, case-control, and cross-sectional studies in PubMed, Embase, and Web of Science, and summarize the associated factors of myopic CNV using meta-analysis where applicable. Among 1,333 records assessed, 50 were found eligible, all having a low-to-moderate risk of bias. Highly myopic eyes with CNV had a higher risk of lacquer cracks (odds ratio = 2.88) and patchy chorioretinal atrophy (odds ratio = 3.43) than those without. The mean posterior staphyloma height (µm) was greater in myopic CNV eyes than in highly myopic eyes without CNV (mean difference = 82.03). The thinning of choroidal thickness (µm) between myopic eyes with and without CNV differed significantly (mean difference = -47.76). The level of vascular endothelial growth factor (pg/ml) in the aqueous humor of myopic CNV eyes was significantly higher than in highly myopic eyes without CNV (mean difference = 24.98), the same as interleukin-8 (IL-8) (pg/ml, mean difference = 7.73). Single-nucleotide polymorphisms in the vascular endothelial growth factor, complement factor I, and collagen type VIII alpha 1 genes were associated with myopic CNV. We found that myopic CNV eyes have a higher ratio of lacquer cracks and patchy chorioretinal atrophy, thinner choroid, greater posterior staphyloma height, and a higher level of vascular endothelial growth factor and IL-8 in aqueous. Structural predisposing lesions, hemodynamic, genetic, and systemic factors are also associated with myopic CNV.

Predicting diabetic kidney disease for type 2 diabetes mellitus by machine learning in the real world: a multicenter retrospective study.

Objective: Diabetic kidney disease (DKD) has been reported as a main microvascular complication of diabetes mellitus. Although renal biopsy is capable of distinguishing DKD from Non Diabetic kidney disease(NDKD), no gold standard has been validated to assess the development of DKD.This study aimed to build an auxiliary diagnosis model for type 2 Diabetic kidney disease (T2DKD) based on machine learning algorithms. Methods: Clinical data on 3624 individuals with type 2 diabetes (T2DM) was gathered from January 1, 2019 to December 31, 2019 using a multi-center retrospective database. The data fell into a training set and a validation set at random at a ratio of 8:2. To identify critical clinical variables, the absolute shrinkage and selection operator with the lowest number was employed. Fifteen machine learning models were built to support the diagnosis of T2DKD, and the optimal model was selected in accordance with the area under the receiver operating characteristic curve (AUC) and accuracy. The model was improved with the use of Bayesian Optimization methods. The Shapley Additive explanations (SHAP) approach was used to illustrate prediction findings. Results: DKD was diagnosed in 1856 (51.2 percent) of the 3624 individuals within the final cohort. As revealed by the SHAP findings, the Categorical Boosting (CatBoost) model achieved the optimal performance 1in the prediction of the risk of T2DKD, with an AUC of 0.86 based on the top 38 characteristics. The SHAP findings suggested that a simplified CatBoost model with an AUC of 0.84 was built in accordance with the top 12 characteristics. The more basic model features consisted of systolic blood pressure (SBP), creatinine (CREA), length of stay (LOS), thrombin time (TT), Age, prothrombin time (PT), platelet large cell ratio (P-LCR), albumin (ALB), glucose (GLU), fibrinogen (FIB-C), red blood cell distribution width-standard deviation (RDW-SD), as well as hemoglobin A1C(HbA1C). Conclusion: A machine learning-based model for the prediction of the risk of developing T2DKD was built, and its effectiveness was verified. The CatBoost model can contribute to the diagnosis of T2DKD. Clinicians could gain more insights into the outcomes if the ML model is made interpretable.

Isolation of Hv-CRKP with co-production of three carbapenemases (blaKPC, blaOXA-181 or OXA-232, and blaNDM-1) and a virulence plasmid: a study from a Chinese tertiary hospital.

Background: The worldwide dissemination of K. pneumoniae isolates is a significant public health concern, as these organisms possess a unique capacity to acquire genetic elements encoding both resistance and hypervirulence. This study aims to investigate the epidemiological, resistance, and virulence characteristics of K. pneumoniae isolates that carry both virulence plasmids and blaOXA-48-like genes in a tertiary hospital in China. Methods: A total of 217 clinical isolates of carbapenem-resistant K. pneumoniae (CRKP) were collected between April 2020 and March 2022. The antimicrobial susceptibility test was conducted to evaluate the drug resistance profile. All isolates were screened for the presence of genes encoding carbapenemases (blaKPC, blaNDM, blaIMP, blaVIM, and blaOXA-48-like), ESBLs genes (blaCTX-M, blaSHV, blaTEM), and virulence plasmid pLVPK-borne genes (rmpA, rmpA2, iucA, iroB, and peg344) using polymerase chain reaction (PCR) amplification. Clonal lineages were assigned using multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). The plasmid incompatibility groups were identified using PCR-based replicon typing (PBRT). The transferability of carbapenemase-encoding plasmids and pLVPK-like virulence plasmids was assessed via conjugation. The plasmid location of rmpA2 was determined using S1-Pulsed Field Gel Electrophoresis (S1-PFGE) and southern blotting hybridization. The virulence potential of the isolates was assessed using the string test, capsular serotyping, serum killing assay and a Galleria mellonella larval infection model. Results: Of the 217 CRKP clinical isolates collected, 23% were identified as carrying blaOXA-48-like genes. All blaOXA-48-like isolates exhibited resistance to commonly used clinical antimicrobial agents, except for ceftazidime/avibactam, colistin, tigecycline, trimethoprim-sulfamethOXAzole, polymyxin B, and nitrofurantoin. The main common OXA-48-like carbapenemase enzymes were found to be blaOXA-181 and blaOXA-232. MLST and PFGE fingerprinting analysis revealed clonal transmission and plasmid transmission. OXA-48-like producing CRKP isolates mainly clustered in K64 ST11 and K47 ST15. Results of the string Test, serum killing assay (in vitro) and Galleria mellonella infection model (in vivo) indicated hypervirulence. PBRT showed that the blaOXA-181 and blaOXA-232 producing hypervirulent carbapenem-resistant Klebsiella pneumoniae (Hv-CRKP) were mainly carried on ColE-type, IncF, and IncX3. Eight clinical isolates of hv-CRKP were identified as carrying three carbapenem-resistant genes (blaKPC, blaOXA-181 or OXA-232, and blaNDM-1). Moreover, Southern blotting hybridization revealed that all eight isolates had a pLVPK-like virulent plasmid (138.9-216.9 kb) with an uneven number and size of plasmid. Conclusion: In our investigation, we have observed the emergence of hv-CRKP carrying blaOXA-48-like genes, which identified two genetic relationships: clonal transmission and plasmid transmission. PBRT analysis showed that these genes were mainly carried on ColE-type, IncF, and IncX3 plasmids. These isolates have been shown to be hypervirulent in vitro and in vivo. Additionally, eight clinical isolates of hv-CRKP were identified as carrying three carbapenem-resistant genes (blaKPC, blaOXA-181 or OXA-232, and blaNDM-1) and carrying a pLVPK-like virulent plasmid. Hence, our findings highlight the need for further investigation and active surveillance of hypervirulent OXA-48-like producing Hv-CRKP isolates to control their transmission.

Impact of physical and mental fatigue on construction workers' unsafe behavior based on physiological measurement.

INTRODUCTION: Construction worker fatigue is an important factor leading to unsafe behavior, a major cause of construction accidents. Uncovering the impact mechanism of fatigue on workers' unsafe behavior can prevent construction accidents. However, it is difficult to effectively measure workers' fatigue onsite and analyze the impact of worker fatigue on their unsafe behavior. METHOD: This research analyzes the relationship between the physical and mental fatigue of construction workers and their unsafe behavior via physiological measurement based on a simulated experiment on handling tasks. RESULTS: It is found that: (a) both physical fatigue and mental fatigue have negative effects on workers' cognitive ability and motion ability, and the negative effects are more serious under the combination of the two types of fatigue; (b) mental fatigue can easily change workers' risk propensity, making them more willing to face risks, and in a state of the two types of fatigue, they are more likely to make choices with less pay and higher risk; (c) the number of signal identification errors is positively correlated with LF (low frequency)/HF (high frequency), and negatively correlated with the standard deviation of normal-to-normal intervals (SDNN), while the number of footstep control errors is negatively correlated with the time elapsed between two successive R waves (RR interval) and skin temperature (SKT). PRACTICAL APPLICATIONS: These findings can enrich construction safety management theory from a perspective of quantified fatigue and facilitate safety management practices on construction sites, thus contributing to the body of knowledge and practices of construction safety management.

Radioactive and Fluorescent Dual Modality Cysteine Cathepsin B Activity-Based Probe for Cancer Theranostics.

Cysteine cathepsin B (CTS-B) is a crucial enzyme that is overexpressed in numerous malignancies and contributes to the invasion and metastasis of cancer. Therefore, this study sets out to develop and evaluate an activity-based multimodality theranostic agent targeting CTS-B for cancer imaging and therapy. A CTS-B activity-based probe, BMX2, was synthesized and labeled efficiently with 68Ga and 90Y to produce 68Ga-BMX2 for multimodality imaging and 90Y-BMX2 for radiation therapy. The affinity and specificity of BMX2 binding with the CTS-B enzyme were determined by fluorescent western blots using recombined active human CTS-B enzyme (rh-CTS-B) and four cancer cell lines including HeLa, HepG2, MCF7, and U87MG, with CA074 as the CTS-B inhibitor for control. Confocal laser scanning microscope imaging and cell uptake measurement were also performed. Then, in vivo PET imaging and fluorescence imaging were acquired on HeLa xenografts. Finally, the therapeutic effect of 90Y-BMX2 was tested. BMX2 could be specifically activated by rh-CTS-B and stably bound to the enzyme. The binding of BMX2 with CTS-B is time-dependent and enzyme concentration-dependent. Although CTS-B expression varied between cell lines, all showed significant uptake of BMX2 and 68Ga-BMX2. In vivo optical and PET imaging showed a high tumor uptake of BMX2 and 68Ga-BMX2 and accumulation for more than 24 h. 90Y-BMX2 could significantly inhibit HeLa tumor growth. The development of 68Ga/90Y-BMX2, a radioactive and fluorescent dual modality theranostic agent, demonstrated an effective theranostic approach for PET diagnostic imaging, fluorescence imaging, and radionuclide therapy of cancers, which may have a potential for clinical translation for cancer theranostics in the future.

Identifying therapeutic biomarkers of zoledronic acid by metabolomics.

Zoledronic acid (ZOL) is a potent antiresorptive agent that increases bone mineral density (BMD) and reduces fracture risk in postmenopausal osteoporosis (PMOP). The anti-osteoporotic effect of ZOL is determined by annual BMD measurement. In most cases, bone turnover markers function as early indicators of therapeutic response, but they fail to reflect long-term effects. We used untargeted metabolomics to characterize time-dependent metabolic shifts in response to ZOL and to screen potential therapeutic markers. In addition, bone marrow RNA-seq was performed to support plasma metabolic profiling. Sixty rats were assigned to sham-operated group (SHAM, n = 21) and ovariectomy group (OVX, n = 39) and received sham operation or bilateral ovariectomy, respectively. After modeling and verification, rats in the OVX group were further divided into normal saline group (NS, n = 15) and ZOL group (ZA, n = 18). Three doses of 100 µg/kg ZOL were administrated to the ZA group every 2 weeks to simulate 3-year ZOL therapy in PMOP. An equal volume of saline was administered to the SHAM and NS groups. Plasma samples were collected at five time points for metabolic profiling. At the end of the study, selected rats were euthanatized for bone marrow RNA-seq. A total number of 163 compound were identified as differential metabolites between the ZA and NS groups, including mevalonate, a critical molecule in target pathway of ZOL. In addition, prolyl hydroxyproline (PHP), leucyl hydroxyproline (LHP), 4-vinylphenol sulfate (4-VPS) were identified as differential metabolites throughout the study. Moreover, 4-VPS negatively correlated with increased vertebral BMD after ZOL administration as time-series analysis revealed. Bone marrow RNA-seq showed that the PI3K-AKT signaling pathway was significantly associated with ZOL-mediated changes in expression (adjusted-p = 0.018). In conclusion, mevalonate, PHP, LHP, and 4-VPS are candidate therapeutic markers of ZOL. The pharmacological effect of ZOL likely occurs through inhibition of the PI3K-AKT signaling pathway.

Studies on Cistanches Herba: A Bibliometric Analysis.

As a famous tonic herb, Cistanches Herba is known for its broad medicinal functions, especially its hormone balancing, anti-aging, anti-dementia, anti-tumor, anti-oxidative, neuroprotective, and hepatoprotective effects. This study aims to provide a comprehensive bibliometric analysis of studies on Cistanche and to identify research hotspots and frontier topics on the genus. Based on the metrological analysis software CiteSpace, 443 Cistanche related papers were quantitatively reviewed. The results indicate that 330 institutions from 46 countries have publications in this field. China was the leading country in terms of research importance and number of publication (335 articles). In the past decades, studies on Cistanche have mainly focused on its rich active substances and pharmacological effects. Although the research trend shows that Cistanche has grown from an endangered species to an important industrial plant, its breeding and cultivation continue to be important areas for research. In the future, the application of Cistanche species as functional foods may be a new research trend. In addition, active collaborations among researchers, institutions, and countries are expected.

Apocynum venetum, a medicinal, economical and ecological plant: a review update.

Apocynum venetum L. is an important medicinal perennial rhizome plant with good ecological and economic value. Its leaves have many pharmacological effects such as anti-inflammatory, anti-depression, anti-anxiolytic, etc., while its fibers have the title of "king of wild fibers". Furthermore, it was suitable for the restoration of degraded saline soil in arid areas. An increasing studies have been published in the past years. A scientometric analysis was used to analyze the publications of Apocynum venetum L. to clearly review the pharmacology, fiber application of Apocynum venetum L. and the potential value with its similar species (Apocynum pictum Schrenk) to the environment.

Water-Induced Single-Crystal to Single-Crystal Transformation of Ionic Hydrogen-Bonded Organic Frameworks with Enhanced Proton Conductivity.

Two ionic hydrogen-bonded organic frameworks (iHOF-10, iHOF-11) were prepared using 1,1'-diamino-4,4'-bipyridine diiodide (Dbpy ⋅ 2I) and tetrakis(4-sulfophenyl)ethylene (H4 TPE). With increasing RH and temperature, water molecules induce single crystal to single crystal (SCSC) transformation of iHOF-10, resulting in the formation of iHOF-11. At 90 °C, 98 % RH, the proton conductivity of iHOF-11 (7.03×10-3  S cm-1 ) is 2.09 times higher than iHOF-10 (3.37×10-3  S cm-1 ). At 50 °C, 98 % RH, iHOF-11 (9.49×10-4  S cm-1 ) is 19.06 times higher than iHOF-10 (4.98×10-5  S cm-1 ). The proton conductivity shows water molecules enter the crystal and induce crystal transformation and reorganization of the hydrogen bonding structure, thus increasing the proton conductivity and stability.