Chih-Hui Yang

Summary While FRAX with BMD could be more precise in estimating the fracture risk, DL-based models were validated to slightly reduce the number of under- and over-treated patients when no BMD measurements were available. The validated models could be used to screen for patients at a high risk of fracture and osteoporosis. Purpose Fracture risk assessment tool (FRAX) is useful in classifying the fracture risk level, and precise prediction can be achieved by estimating both clinical risk factors and bone mineral density (BMD) using dual X-ray absorptiometry (DXA). However, DXA is not frequently feasible because of its cost and accessibility. This study aimed to establish the reliability of deep learning (DL)-based alternative tools for screening patients at a high risk of fracture and osteoporosis. Methods Participants were enrolled from the National Bone Health Screening Project of Taiwan in this cross-sectional study. First, DL-based models were built to predict the lowest T-score value in either the lumbar spine, total hip, or femoral neck and their respective BMD values. The Bland–Altman analysis was used to compare the agreement between the models and DXA. Second, the predictive model to classify patients with a high fracture risk was built according to the estimated BMD from the first step and the FRAX score without BMD. The performance of the model was compared with the classification based on FRAX with BMD. Results Approximately 10,827 women (mean age, 65.4 ± 9.4 years) were enrolled. In the prediction of the lumbar spine BMD, total hip BMD, femoral neck BMD, and lowest T-score, the root-mean-square error (RMSE) was 0.099, 0.089, 0.076, and 0.68, respectively. The Bland–Altman analysis revealed a nonsignificant difference between the predictive models and DXA. The FRAX score with femoral neck BMD for major osteoporotic fracture risk was 9.7% ± 6.7%, whereas the risk for hip fracture was 3.3% ± 4.6%. Comparison between the classification of FRAX with and without BMD revealed the accuracy rate, positive predictive value (PPV), and negative predictive value (NPV) of 78.8%, 64.6%, and 89.9%, respectively. The area under the receiver operating characteristic curve (AUROC), accuracy rate, PPV, and NPV of the classification model were 0.913 (95% confidence interval: 0.904–0.922), 83.5%, 71.2%, and 92.2%, respectively. Conclusion While FRAX with BMD could be more precise in estimating the fracture risk, DL-based models were validated to slightly reduce the number of under- and over-treated patients when no BMD measurements were available. The validated models could be used to screen for patients at a high risk of fracture and osteoporosis.

Our previous findings have shown that the chlorophyllides composites have anticancer activities to breast cancer cell lines (MCF-7 and MDA-MB-231). In the present study, microarray gene expression profiling was utilized to investigate the chlorophyllides anticancer mechanism on the breast cancer cells lines. Results showed that chlorophyllides composites induced upregulation of 43 and 56 differentially expressed genes (DEG) in MCF-7 and MDA-MB-231 cells, respectively. In both cell lines, chlorophyllides composites modulated the expression of annexin A4 (ANXA4), chemokine C-C motif receptor 1 (CCR1), stromal interaction molecule 2 (STIM2), ethanolamine kinase 1 (ETNK1) and member of RAS oncogene family (RAP2B). Further, the KEGG annotation revealed that chlorophyllides composites modulated DEGs that are associated with the endocrine system in MCF-7 cells and with the nervous system in MDA-MB-231 cells, respectively. The expression levels of 9 genes were validated by quantitative reverse transcription PCR (RT-qPCR). The expression of CCR1, STIM2, ETNK1, MAGl1 and TOP2A were upregulated in both chlorophyllides composites treated-MCF-7 and MDA-MB-231 cells. The different expression of NLRC5, SLC7A7 and PKN1 provided valuable information for future investigation and development of novel cancer therapy.

Background. Chronic kidney disease (CKD) is a critical public health issue with a huge financial burden for both patients and society worldwide. Unfortunately, there are currently no efficacious therapies to prevent or delay the progression of end-stage renal disease (ESRD). Traditional Chinese medicine practices have shown that Cordyceps militaris (C. militaris) mycelia have a variety of pharmacologically useful properties, including antitumor, immunomodulation, and hepatoprotection. However, the effect of mycelial C. militaris on CKD remains unclear. Methods. Here, we investigated the effects of C. militaris mycelia on mice with CKD using four types of media: HKS, HKS with vitamin A (HKS+A), CM, and CM with vitamin A (CM+A). Results. The results at day 10 revealed that the levels of blood urea nitrogen (BUN) were significantly lower in the HKS (41), HKS+A (41), and CM+A (34) groups compared with those in the corresponding control groups (nephrectomic mice). The level of serum creatinine in the HKS+A group decreased by 35 at day 10, whereas the levels in the HKS and CM+A groups decreased only by 14 and 13, respectively, on day 30. Taken together, this is the first report using four new media (HKS, HKS+A, CM, and CM+A medium) for C. militaris mycelia. Each medium of mycelial C. militaris on CKD exhibits specific effect on BUN, serum creatinine, body weight, total protein, and uric acid. Conclusions. Taken together, this is the first report using four new media (HKS, HKS+A, CM, and CM+A medium) for C. militaris mycelia. Each medium of mycelial C. militaris on CKD exhibits specific effects on BUN, serum creatinine, body weight, total protein, and uric acid. We concluded that treatment with C. militaris mycelia cultured in HKS or CM+A medium could potentially prevent the deterioration of kidney function in mice with CKD.

Magnetite nanoparticles (MNPs) represent one of the most intensively studied types of iron oxide nanoparticles in various fields, including biomedicine, pharmaceutics, bioengineering, and industry. Since their properties in terms of size, shape, and surface charge significantly affects their efficiency towards the envisaged application, it is fundamentally important to develop a new synthesis route that allows for the control and modulation of the nanoparticle features. In this context, the aim of the present study was to develop a new method for the synthesis of MNPs. Specifically, a microfluidic lab-on-chip (LoC) device was used to obtain MNPs with controlled properties. The study investigated the influence of iron precursor solution concentration and flowed onto the final properties of the nanomaterials. The synthesized MNPs were characterized in terms of size, morphology, structure, composition, and stability. Results proved the formation of magnetite as a single mineral phase. Moreover, the uniform spherical shape and narrow size distribution were demonstrated. Optimal characteristics regarding MNPs crystallinity, uniformity, and thermal stability were obtained at higher concentrations and lower flows. In this manner, the potential of the LoC device is a promising tool for the synthesis of nanomaterials by ensuring the necessary uniformity for all final applications.

Chlorophyllides can be found in photosynthetic organisms. Generally, chlorophyllides have a-, b-, c-, d-, and f-type derivatives, and all chlorophyllides have a tetrapyrrole structure with a Mg ion at the center and a fifth isocyclic pentanone. Chlorophyllide a can be synthesized from protochlorophyllide a, divinyl chlorophyllide a, or chlorophyll. In addition, chlorophyllide a can be transformed into chlorophyllide b, chlorophyllide d, or chlorophyllide f. Chlorophyllide c can be synthesized from protochlorophyllide a or divinyl protochlorophyllide a. Chlorophyllides have been extensively used in food, medicine, and pharmaceutical applications. Furthermore, chlorophyllides exhibit many biological activities, such as anti-growth, antimicrobial, antiviral, antipathogenic, and antiproliferative activity. The photosensitivity of chlorophyllides that is applied in mercury electrodes and sensors were discussed. This article is the first detailed review dedicated specifically to chlorophyllides. Thus, this review aims to describe the definition of chlorophyllides, biosynthetic routes of chlorophyllides, purification of chlorophyllides, and applications of chlorophyllides.

The purity of chlorophylls plays one of the key role for the production of chlorophyllides. We have designed a facile method for chlorophyll purification by twice solvent extraction. Twice extraction causes the loss of chlorophylls, but the purity of total chlorophylls can be enhanced 182%. Then, the purified chlorophylls can be converted to relatively pure chlorophyllides facilely. The results show that higher purity of chlorophyllides could be obtained when purified chlorophylls (ethanol-hexane extract) was used as starting materials than that of crude chlorophylls (ethanol-only extract). In biocompatibility test, the results showed that the prepared chlorophyllides can be applied as biomaterials. When the prepared chlorophyllides were applied to anticancer tests, they were active both in MCF7 and MDA-MB-231 (multidrug resistant breast cancer cells) cell lines. In addition, the results suggested that the prepared chlorophyllides could be a potential candidate of combination therapy with doxorubicin to breast cancers.

Generally, bacteriochlorophyllides were responsible for the photosynthesis in bacteria. Seven types of bacteriochlorophyllides have been disclosed. Bacteriochlorophyllides a/b/g could be synthesized from divinyl chlorophyllide a. The other bacteriochlorophyllides c/d/e/f could be synthesized from chlorophyllide a. The chemical structure and synthetic route of bacteriochlorophyllides were summarized in this review. Furthermore, the potential applications of bacteriochlorophyllides in photosensitizers, immunosensors, influence on bacteriochlorophyll aggregation, dye-sensitized solar cell, heme synthesis and for light energy harvesting simulation were discussed.

Cordyceps militaris (C. militaris) is a fungus with a long history of widespread use in folk medicine, and its biological and medicinal functions are well studied. A crucial pharmacological effect of C. militaris is immunomodulation. In this review, we catalog the immunomodulatory effects of different extracts of C. militaris, namely total extracts, polysaccharides and cordycepin. Total extracts obtained using water or 50% ethyl alcohol and polysaccharides from C. militaris were discovered to tend to promote type 1 immunity, whereas total extracts obtained using 70–80% ethyl alcohol and cordycepin from C. militaris were more likely to promote type 2 immunity. This article is the first to classify the immunomodulatory effects of different extracts of C. militaris. In addition, we discovered a relationship between different segments or extracts and differing types of immunity. This review can provide the readers a comprehensive understanding on the immunomodulatory effects of the precious folk medicine and guidance on its use for both health people and those with an immunodeficiency.

We fabricated nanomaterials comprising amino-functionalized and nitrogen-doped graphene quantum dots (amino-N-GQDs) and investigated their photostability and intrinsic luminescence in the near-infrared spectrum to determine their suitability as contrast agents in two-photon imaging (TPI). We observed that amino-N-GQDs with a higher amount of bonded nitrogen and amino-functionalized groups (6.2%) exhibited superior two-photon properties to those with a lower amount of such nitrogen and groups (4.9%). These materials were conjugated with polymers containing sulfur (polystyrene sulfonate, PSS) and nitrogen atoms (polyethylenimine, PEI), forming amino-N-GQD–PSS–PEI specimens (amino-N-GQD-polymers). The polymers exhibited a high quantum yield, remarkable stability, and notable two-photon properties and generated no reactive oxygen species, rendering them excellent two-photon contrast agents for bioimaging. An antiepidermal growth factor receptor (Ab_EGFR) was used for labeling to increase specificity. Two-photon imaging (TPI) of amino-N-GQD (6.2%)-polymer-Ab_EGFR-treated A431 cancer cells revealed remarkable brightness, intensity, and signal-to-noise ratios for each observation at a two-photon excitation power of 16.9 nJ pixel⁻¹ under 30 scans and a three-dimensional (3D) depth of 105 µm, indicating that amino-N-GQD (6.2%)-polymer-Ab_EGFR-treated cells can achieve two-photon luminescence with 71 times less power required for two-photon autofluorescence (1322.8 nJ pixel⁻¹ with 500 scans) of similar intensity. This economy can minimize photodamage to cells, rendering amino-N-GQD-polymers suitable for noninvasive 3D bioimaging.