Biological Evaluations, NMR Analyses, Molecular Modeling Studies, and Overview of the Synthesis of the Marine Natural Product (-)-Mucosin.

Natural products obtained from marine organisms continue to be a rich source of novel structural architecture and of importance in drug discovery, medicine, and health. However, the success of such endeavors depends on the exact structural elucidation and access to sufficient material, often by stereoselective total synthesis, of the isolated natural product of interest. (-)-Mucosin (1), a fatty acid derivative, previously presumed to contain a rare cis-bicyclo[4.3.0]non-3-ene moiety, has since been shown to be the trans-congener. Analytically, the fused bicyclic ring system in (-)-1 constitutes a particular challenge in order to establish its relative and absolute stereochemistry. Herein, data from biological evaluations, NMR and molecular modeling studies of (-)-1 are presented. An overview of the synthetic strategies enabling the exact structural elucidation of (-)-mucosin (1) is also presented.

PCDHGB7 hypermethylation-based Cervical cancer Methylation (CerMe) detection for the triage of high-risk human papillomavirus-positive women: a prospective cohort study.

BACKGROUND: Implementation of high-risk human papillomavirus (hrHPV) screening has greatly reduced the incidence and mortality of cervical cancer. However, a triage strategy that is effective, noninvasive, and independent from the subjective interpretation of pathologists is urgently required to decrease unnecessary colposcopy referrals in hrHPV-positive women. METHODS: A total of 3251 hrHPV-positive women aged 30-82 years (median = 41 years) from International Peace Maternity and Child Health Hospital were included in the training set (n = 2116) and the validation set (n = 1135) to establish Cervical cancer Methylation (CerMe) detection. The performance of CerMe as a triage for hrHPV-positive women was evaluated. RESULTS: CerMe detection efficiently distinguished cervical intraepithelial neoplasia grade 2 or worse (CIN2 +) from cervical intraepithelial neoplasia grade 1 or normal (CIN1 -) women with excellent sensitivity of 82.4% (95% CI = 72.6 ~ 89.8%) and specificity of 91.1% (95% CI = 89.2 ~ 92.7%). Importantly, CerMe showed improved specificity (92.1% vs. 74.9%) in other 12 hrHPV type-positive women as well as superior sensitivity (80.8% vs. 61.5%) and specificity (88.9% vs. 75.3%) in HPV16/18 type-positive women compared with cytology testing. CerMe performed well in the triage of hrHPV-positive women with ASC-US (sensitivity = 74.4%, specificity = 87.5%) or LSIL cytology (sensitivity = 84.4%, specificity = 83.9%). CONCLUSIONS: PCDHGB7 hypermethylation-based CerMe detection can be used as a triage strategy for hrHPV-positive women to reduce unnecessary over-referrals. TRIAL REGISTRATION: ChiCTR2100048972. Registered on 19 July 2021.

A pH-responsive cetuximab-conjugated DMAKO-20 nano-delivery system for overcoming K-ras mutations and drug resistance in colorectal carcinoma.

Cetuximab (Cet) and oxaliplatin (OXA) are used as first-line drugs for patients with colorectal carcinoma (CRC). In fact, the heterogeneity of CRC, mainly caused by K-ras mutations and drug resistance, undermines the effectiveness of drugs. Recently, a hydrophobic prodrug, (1E,4E)-6-((S)-1-(isopentyloxy)-4-methylpent-3-en-1-yl)-5,8-dimethoxynaphthalene-1,4­dione dioxime (DMAKO-20), has been shown to undergo tumor-specific CYP1B1-catalyzed bioactivation. This process results in the production of nitric oxide and active naphthoquinone mono-oximes, which exhibit specific antitumor activity against drug-resistant CRC. In this study, a Cet-conjugated bioresponsive DMAKO-20/PCL-PEOz-targeted nanocodelivery system (DMAKO@PCL-PEOz-Cet) was constructed to address the issue of DMAKO-20 dissolution and achieve multitargeted delivery of the cargoes to different subtypes of CRC cells to overcome K-ras mutations and drug resistance in CRC. The experimental results demonstrated that DMAKO@PCL-PEOz-Cet efficiently delivered DMAKO-20 to both K-ras mutant and wild-type CRC cells by targeting the epidermal growth factor receptor (EGFR). It exhibited a higher anticancer effect than OXA in K-ras mutant cells and drug-resistant cells. Additionally, it was observed that DMAKO@PCL-PEOz-Cet reduced the expression of glutathione peroxidase 4 (GPX4) in CRC cells and significantly inhibited the growth of heterogeneous HCT-116 subcutaneous tumors and patient-derived tumor xenografts (PDX) model tumors. This work provides a new strategy for the development of safe and effective approaches for treating CRC. STATEMENT OF SIGNIFICANCE: (1) Significance: This work reports a new approach for the treatment of colorectal carcinoma (CRC) using the bioresponsible Cet-conjugated PCL-PEOz/DMAKO-20 nanodelivery system (DMAKO@PCL-PEOz-Cet) prepared with Cet and PCL-PEOz for the targeted transfer of DMAKO-20, which is an anticancer multitarget drug that can even prevent drug resistance, to wild-type and K-ras mutant CRC cells. DMAKO@PCL-PEOz-Cet, in the form of nanocrystal micelles, maintained stability in peripheral blood and efficiently transported DMAKO-20 to various subtypes of colorectal carcinoma cells, overcoming the challenges posed by K-ras mutations and drug resistance. The system's secure and effective delivery capabilities have also been confirmed in organoid and PDX models. (2) This is the first report demonstrating that this approach simultaneously overcomes the K-ras mutation and drug resistance of CRC.

Alkaline humic acid fertilizer alters the distribution, availability, and translocation of cadmium and zinc in the acidic soil-Sauropus androgynus system.

Humic acids (HA) are a popular soil additive to reduce metal availability, but they have the drawbacks of reduced effectiveness over time and a significant reduction in soil pH. An alkaline humic acid fertilizer (AHAF) combining alkaline additives with HA was developed to overcome such drawbacks. A field experiment was conducted to investigate the effects of different AHAF application rates on the physicochemical properties, bioavailability, accumulation, and translocation of Cd and Zn heavy metals in Sauropus androgynus grown in acidic soil. Based on our results, the 100AF (100% AHAF) treatment significantly increased soil pH, cation exchange capacity (CEC), and organic matter content (OM) after one year of application. Compared with the control treatment (CK), the application of different rates of AHAF resulted in a 37.1-40.3% decrease in soil exchangeable Cd fractions (Exc-Cd) and an increase in the humic acid-bound Cd fractions (HA-Cd) Fe- and Mn-oxide-bound Cd fractions (OX-Cd), and organic matter-bound Cd fractions (OM-Cd) by 9.5-64.6%, 24.8-45.1%, and 158.8-191.2%, respectively (P < 0.05). The different AHAF treatments decreased the Res-Zn, Exc-Zn, and OM-Zn fractions by 69.6-73.0%, 7.4-23.9%, and 18.1-23.2%, respectively (P < 0.05), and increased the HA-Zn fraction by 8.4-28.1%. In the control treatment, the bioconcentration factors (BCFs) for Cd and Zn in different S. androgynus plant organs were in the following order: (Cd) Leaves > Stems > Branches > Roots > Edible branches; (Zn) Roots > Stems > Leaves > Branches > Edible branches. The transfer factors (TFs) of Cd and Zn in S. androgynus were classified as follows: TF2 > TF1 > TF3 > TF4. Thus, S. androgynus stems, and roots had a strong ability to transport Cd and Zn to the leaves. Compared with CK, the 100AF treatment significantly increased the BCFs for Zn in all plant parts (except BCFedible branches). In contrast, it significantly decreased all BCFs and TFs for Cd and the TF4 for Zn, effectively reducing Cd and Zn accumulation in the edible branches of S. androgynus. Soil pH, CEC, OM, and HA-M fraction were highly and significantly negatively correlated with Cd and Zn content in edible branches (P < 0.001). Stepwise multiple linear regression analysis revealed that the soil HA-M fraction was the key contributing factor for Zn accumulation and translocation in S. androgynus. Moreover, based on our findings, the absorption, uptake, and translocation of Cd and Zn were mainly determined by metal speciation and the pH in the soil. Moreover, the competitive antagonistic mechanisms between Zn and Cd absorption also affected their accumulation in S. androgynus. Thus, AHAF can be used as a soil amendment to sustainably improve acidic soils and effectively reduce Cd and Zn accumulation in edible branches of S. androgynus.

TRPS1 regulates the opposite effect of progesterone via RANKL in endometrial carcinoma and breast carcinoma.

Medroxyprogesterone (MPA) has therapeutic effect on endometrial carcinoma (EC), while it could promote the carcinogenesis of breast cancer (BC) by activating receptor activator of NF-kB ligand (RANKL). However, the selective mechanism of MPA in endometrium and breast tissue remains obscure. Multiomics analysis of chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) were performed in cell lines derived from endometrial cancer and mammary tumor to screen the differential co-regulatory factors of progesterone receptor (PR). Dual-luciferase assays and ChIP-PCR assays were used to validate the transcriptional regulation. Co-immunoprecipitation (Co-IP) and immunofluorescence assays were carried out to explore molecular interactions between PR, the cofactor transcriptional repressor GATA binding 1 (TRPS1), and histone deacetylase 2 (HDAC2). Subsequently, human endometrial cancer/breast cancer xenograft models were established to investigate the regulation effect of cofactor TRPS1 in vivo. In the current study, we found that MPA downregulated RANKL expression in a time- and dose-dependent manner in EC, while had the opposite effect on BC. Then PR could recruit cofactor TRPS1 to the promoter of RANKL, leading to histone deacetylation of RANKL to repress its transcription in EC, whereas MPA disassociated the PR/TRPS1/HDAC2 complex to enhance RANKL histone acetylation in BC. Therefore, TRPS1, the coregulator recruited by PR played a critical role in the selective mechanism of progesterone in EC and BC and could become a potential candidate for targeted therapy to improve the anticancer effect of MPA on EC and avoid its carcinogenic effect on BC.

Precision Therapy of Recurrent Breast Cancer through Targeting Different Malignant Tumor Cells with a HER2/CD44-Targeted Hydrogel Nanobot.

Heterogeneity and drug resistance of tumor cells are the leading causes of incurability and poor survival for patients with recurrent breast cancer. In order to accurately deliver the biological anticancer drugs to different subtypes of malignant tumor cells for omnidirectional targeted treatment of recurrent breast cancer, a distinct design is demonstrated by embedding liposome-based nanocomplexes containing pro-apoptotic peptide and survivin siRNA drugs (LPR) into Herceptin/hyaluronic acid cross-linked nanohydrogels (Herceptin-HA) to fabricate a HER2/CD44-targeted hydrogel nanobot (named as ALPR). ALPR delivered cargoes to the cells overexpressing CD44 and HER2, followed by Herceptin-HA biodegradation, subsequently, the exposed lipid component containing DOPE fused with the endosomal membrane and released peptide and siRNA into the cytoplasm. These experiments indicated that ALPR can specifically deliver Herceptin, peptide, and siRNA drugs to HER2-positive SKBR-3, triple-negative MDA-MB-231, and HER2-negative drug-resistant MCF-7 human breast cancer cells. ALPR completely inhibited the growth of heterogeneous breast tumors via multichannel synergistic effects: disrupting mitochondria, downregulating the survivin gene, and blocking HER2 receptors on the surface of HER2-positive cells. The present design overcomes the chemical drug resistance and opens a feasible route for the combinative treatment of recurrent breast cancer, even other solid tumors, utilizing different kinds of biological drugs.

Construction of a CCL20-centered circadian-signature based prognostic model in cervical cancer.

BACKGROUND: Rather low vaccination rates for Human papillomavirus (HPV) and pre-existing cervical cancer patients with limited therapeutic strategies ask for more precise prognostic model development. On the other side, the clinical significance of circadian clock signatures in cervical cancer lacks investigation. METHODS: Subtypes classification based upon eight circadian clock core genes were implemented in TCGA-CESC through k-means clustering methods. Afterwards, KEGG, GO and GSEA analysis were conducted upon differentially expressed genes (DEGs) between high and low-risk groups, and tumor microenvironment (TME) investigation by CIBERSORT and ESTIMATE. Furthermore, a prognostic model was developed by cox and lasso regression methods, and verified in GSE44001 by time-dependent receiver-operating characteristic curve (ROC) analysis. Lastly, FISH and IHC were used for validation of CCL20 expression in patients' specimens and U14 subcutaneous tumor models were built for TME composition. RESULTS: We successfully classified cervical patients into high-risk and low-risk groups based upon circadian-oscillation-signatures. Afterwards, we built a prognostic risk model composed of GJB2, CCL20 and KRT24 with excellent predictive value on patients' overall survival (OS). We then proposed metabolism unbalance, especially for glycolysis, and immune related pathways to be major enriched signatures between the high-risk and low-risk groups. Then, we proposed an 'immune-desert'-like suppressive myeloid cells infiltration pattern in high-risk group TME and verified its resistance to immunotherapies. Finally, CCL20 was proved positively correlated with real-world patients' stages and induced significant less CD8+ T cells and more M2 macrophages infiltration in mouse model. CONCLUSIONS: We unraveled a prognostic risk model based upon circadian oscillation and verified its solidity. Specifically, we unveiled distinct TME immune signatures in high-risk groups.

Benign metastasizing uterine leiomyoma with lymphatic and pulmonary metastases: a case report and literature review.

BACKGROUND: Benign metastasizing leiomyoma (BML) is a rare disease usually observed in women of reproductive or premenopausal age with a history of uterine myomectomy or hysterectomy. The most common sites of metastases are the pulmonary, and other sites include heart, bones, liver, lymph nodes, bladder, skeletal muscles, and central nervous system. Here, we report a case of a 50 year-old woman with a history of hysterectomy who was initially suspected of uterine sarcoma but was finally confirmed to have BML with lung and lymph node metastases, and discuss the treatment and prognosis of BML. CASE PRESENTATION: A 50 year-old woman with a history of total abdominal hysterectomy presented with mild but persistent abdominal pain for more than 3 months. She was suspected of having uterine sarcoma before surgery and laparoscopic extensive debulking surgery including bilateral oophorectomy, pelvic and para-aortic lymph node dissection to the level of the left renal vein, and transcutaneous dissection of the right inguinal lymph nodes. Pathology confirmed a benign leiomyoma, and the patient was diagnosed with BML. No medication was administered after the surgery, and the follow-up was of no significance. CONCLUSION: Benign metastasizing leiomyoma (BML) is a rare disorder in which histologically benign smooth muscle tumors metastasize to extrauterine sites. Metastases are commonly observed in the lung, liver, lymph nodes, skin, bladder, esophagus, and skeletal muscles. BML is usually misdiagnosed as a malignant tumor before surgery until the pathology confirms its benign nature. However, this treatment remains controversial and undetermined. The prognosis is usually favorable owing to its benign nature.

Gastric-type mucinous adenocarcinoma of the cervix in a woman with Peutz-Jeghers syndrome: a case report.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder characterized by a predisposition to the development of multiple neoplasms. Gastric-type mucinous adenocarcinoma (GAS), a new variant of carcinoma of the cervix according to 2014 WHO classification, is less common compared with squamous cell carcinoma, is more aggressive and has a lower 5-year survival rate compared with the usual-type endocervical adenocarcinoma, and is also unrelated to human papillomavirus (HPV) infection. CASE SUMMARY: We herein present the case of a 32-year-old patient with PJS who was diagnosed with GAS of the cervix. The patient was not sexually active and had been diagnosed with PJS at 2 years of age. A tumor ∼6 cm was found on the cervix and was diagnosed as GAS of the cervix of clinical-stage IB3. The patient was treated with intra-arterial chemotherapy for one course, followed by radical surgery and then systematic chemotherapy. CONCLUSION: The present case highlights the need for more thorough cancer screening for patients with PJS, as this disorder is rare and is associated with a high risk of malignancies. Young patients with PJS, including those who are not sexually active, who present with watery vaginal discharge or bleeding should be screened for cervical carcinoma, even if the cytological results or HPV tests are negative.

Diagnostic markers of metabolic bone disease of prematurity in preterm infants.

Due to the higher birth rate of preterm infants and improvements in their management, metabolic bone disease of prematurity (MBDP) has a high incidence and is attracting attention. However, clear indicators for the early diagnosis of MBDP are lacking. We aimed to explore simple and feasible early warning indicators for diagnosing MBDP. Our study collected case data of premature infants from two medical centers in Chongqing from January 2020 to February 2022. According to the inclusion and exclusion criteria, data from 136 cases were collected. The correlation between 14 variables in each case and the occurrence of MBDP was analyzed. According to area under the receiver operating characteristic curve (AUROC) analysis, the best cutoff value for each variable was determined. Potential predictors were selected, and Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was used to establish the association of two models with MBDP, whose results were used to develop a diagnostic nomogram. Furthermore, a model decision curve was analyzed. Four predictors were selected from 14 clinical variables by LASSO regression, and Model I was established, including the following characteristics: height (>36 cm), head circumference (≤29.49 cm), total serum calcium (Ca) (>2.13 mmol/L), and alkaline phosphatase (ALP) (>344 U/L) levels. A single predictor, the ALP level (>344 U/L), was used to establish Model II. The AUROC values of the two models were 0.959 for Model I and 0.929 for Model II. In conclusion, in this study, two diagnostic models of MBDP were developed using four combinations of predictors and ALP as a single predictor. Both models showed good sensitivity and specificity for the early diagnosis of metabolic bone disease (MBD), and an ALP level of 344 U/L was defined as a simple and effective diagnostic threshold. In future studies, using larger samples, diagnostic threshold values of ALP for premature infants of different ages should be established, and internal and external validations are needed to improve the adaptability of the current model.

A novel cervix carcinoma biomarker: Pathological-epigenomics, integrated analysis of MethylMix algorithm and pathology for predicting response to cancer immunotherapy.

Herein, A non-invasive pathomics approach was developed to reveal the methylation status in patients with cervical squamous cell carcinoma and predict clinical outcomes and treatment response. Using the MethylMix algorithm, 14 methylation-driven genes were selected for further analysis. We confirmed that methylation-driven genes were differentially expressed in immune, stromal, and tumor cells. In addition, we constructed a methylation-driven model and explored the alterations in immunocyte infiltration between the different models. The methylation-driven subtypes identified in our investigation could effectively predict the clinical outcomes of cervical cancer. To further evaluate the level of methylation-driven patterns, we constructed a risk model with four genes. Significant correlations were observed between the score and immune response markers, including PD1 and CTLA4. Multiple immune infiltration algorithms evaluated the level of immunocyte infiltration between the high- and low-risk groups, while the components of anti-tumor immunocytes in the low-risk group were significantly increased. Subsequently, a total of 205 acquired whole-slide imaging (WSI) images were processed to capture image signatures, and the pathological algorithm was employed to construct an image prediction model based on the risk score classification. The model achieved an area under the curve (AUC) of 0.737 and 0.582 for the training and test datasets, respectively. Moreover, we conducted vitro assays for validation of hub risk gene. The proposed prediction model is a non-invasive method that combines pathomics features and genomic profiles and shows satisfactory performance in predicting patient survival and treatment response. More interdisciplinary fields combining medicine and electronics should be explored in the future.

Daily variations and levels of human chorionic gonadotropin before methotrexate treatment as predictors of treatment success.

AIM: The aim of this study is to investigate the role of human chorionic gonadotropin (hCG) daily variations and levels prior to methotrexate treatment as predictors for treatment outcome. METHODS: This retrospective study included patients who had a sonographically confirmed ectopic pregnancy at the International Peace Maternity and Child Health Hospital between November 2015 and June 2020. The associations of hCG levels and daily variations with the treatment success were evaluated by multivariable logistic regression and receiver operator characteristic (ROC) curve. Establish a nomogram that predicts how methotrexate (MTX) therapy will turn out. The performance of the model was assessed utilizing concordance index, receiver operating characteristic curves, and calibration plots. RESULTS: The median serum hCG levels before treatment and hCG daily variation in the failure group were higher than those in the success group (487.8 vs. 270.7 IU/L, -1.86% vs. 7.29%, both p < 0.01). According to the ROC curve analysis, the cutoff values of serum hCG level before treatment and daily variations were 617.35 IU/L and 1.76%/day. By multivariable logistic regression analysis, serum hCG levels before treatment (odds ratio [OR]: 1.001, 95% confidence interval [CI]: 1.000 ~ 1.001) and hCG daily variations were independently associated with the treatment success (OR: 1.033, 95% CI: 1.015 ~ 1.052). The nomogram was effective at predicting the outcome of MTX treatment with a receiver operating characteristic area under the curve of 0.717 (p < 0.001). The nomogram's calibration curve was almost parallel to the ideal diagonal line. CONCLUSION: We successfully created a nomogram based on serum hCG levels before treatment and hCG daily changes to anticipate the result of MTX therapy, which could assist medical professionals in selecting therapeutic schedule for patients with tubal pregnancies.

Functional mechanisms of TRPS1 in disease progression and its potential role in personalized medicine.

The gene of transcriptional repressor GATA binding 1 (TRPS1), as an atypical GATA transcription factor, has received considerable attention in a plethora of physiological and pathological processes, and may become a promising biomarker for targeted therapies in diseases and tumors. However, there still lacks a comprehensive exploration of its functions and promising clinical applications. Herein, relevant researches published in English from 2000 to 2022 were retrieved from PubMed, Google Scholar and MEDLINE, concerning the roles of TRPS1 in organ differentiation and tumorigenesis. This systematic review predominantly focused on summarizing the structural characteristics and biological mechanisms of TRPS1, its involvement in tricho-rhino-phalangeal syndrome (TRPS), its participation in the development of multiple tissues, the recent advances of its vital features in metabolic disorders as well as malignant tumors, in order to prospect its potential applications in disease detection and cancer targeted therapy. From the clinical perspective, the deeply and thoroughly understanding of the complicated context-dependent and cell-lineage-specific mechanisms of TRPS1 would not only gain novel insights into the complex etiology of diseases, but also provide the fundamental basis for the development of therapeutic drugs targeting both TRPS1 and its critical cofactors, which would facilitate individualized treatment.

Significance of Anoctamin 6 in progression and prognostic prediction of gastric adenocarcinoma.

BACKGROUND: Gastric cancer is one of the most lethal malignancies worldwide with surgery as the only curative therapy. However, postoperative overall survival of gastric cancer is far from satisfactory although significant improvement has been made in adjuvant therapies. Gastric cancer is characterized as highly heterogeneous and illustrating the molecular mechanisms is invaluable for both identification of novel prognostic biomarkers and development of therapeutic drugs. Here we aimed to investigate the participation of Anoctamin 6 (ANO6) in gastric adenocarcinoma. METHODS: Immunohistochemical (IHC) staining was used to explore the expression pattern of ANO6 in tumor tissues from gastric adenocarcinoma patients (n=108). Clinicopathological data was subjected to Kaplan-Meier survival and Cox multivariate analyses to evaluate prognostic predictors. Overexpression and silencing procedures were performed on gastric cancer cell lines to investigate the functional mechanisms of ANO6 in regulating tumor development. RESULTS: Higher ANO6 expression showed a positive correlation with advanced tumor stage of gastric cancer. Univariate and multivariate analyses revealed that ANO6 was an independent prognostic factor for overall survival of gastric cancer. An in vitro study demonstrated that ANO6 can promote cell proliferation while silencing ANO6 significantly downregulated cell viability. CONCLUSION: High ANO6 expression in gastric cancer indicates poor clinical outcomes, and ANO6 may act as a potential target for novel therapy development targeting gastric cancer.

Dynamic trend in alkaline phosphatase activity in infants aged 0-12 months revealed by an indirect approach.

OBJECTIVE: Alkaline phosphatase (ALP) is a ubiquitous enzyme in humans that can be used for diagnosing childhood diseases. Infants have the highest rapid growth rate and are susceptible to metabolic bone diseases. In infants, ALP activities exhibit significant month-wise variations, and authoritative standards are lacking. The present study aimed to provide a reference for the diagnosis of diseases related to abnormal ALP activities in infants. METHODS: This study included 24,618 samples collected from infants aged 0-12 months from three medical centers in Chongqing, China. Samples of infants diagnosed with diseases that may affect ALP activity have been exclude. ALP activity was analyzed using an automatic biochemical analyzer. A percentile curve for ALP activity in male and female infants was constructed using MATLAB, and the skewness-median-coefficient of variation method was employed for curve fitting. RESULTS: ALP activity in male and female infants peaked at 0-4 months; the peak appeared at 1-2 months and declined gradually thereafter. After 4-5 months of age, the ALP activities declined further, with the lowest values observed at 11-12 months of age. A comparison between the data from this study and a those from a published German study indicates that Chinese infants exhibited peak ALP activity later and subsequent decline greater than German infants. CONCLUSIONS: A percentile curve was constructed for month-wise ALP activity in male and female infants, which could provide a reference for diagnosing diseases related to abnormal ALP activity in infants.

Analytical Modeling of a Doubly Clamped Flexible Piezoelectric Energy Harvester with Axial Excitation and Its Experimental Characterization.

With the rapid development of wearable electronics, novel power solutions are required to adapt to flexible surfaces for widespread applications, thus flexible energy harvesters have been extensively studied for their flexibility and stretchability. However, poor power output and insufficient sensitivity to environmental changes limit its widespread application in engineering practice. A doubly clamped flexible piezoelectric energy harvester (FPEH) with axial excitation is therefore proposed for higher power output in a low-frequency vibration environment. Combining the Euler-Bernoulli beam theory and the D'Alembert principle, the differential dynamic equation of the doubly clamped energy harvester is derived, in which the excitation mode of axial load with pre-deformation is considered. A numerical solution of voltage amplitude and average power is obtained using the Rayleigh-Ritz method. Output power of 22.5 µW at 27.1 Hz, with the optimal load resistance being 1 MΩ, is determined by the frequency sweeping analysis. In order to power electronic devices, the converted alternating electric energy should be rectified into direct current energy. By connecting to the MDA2500 standard rectified electric bridge, a rectified DC output voltage across the 1 MΩ load resistor is characterized to be 2.39 V. For further validation of the mechanical-electrical dynamical model of the doubly clamped flexible piezoelectric energy harvester, its output performances, including both its frequency response and resistance load matching performances, are experimentally characterized. From the experimental results, the maximum output power is 1.38 µW, with a load resistance of 5.7 MΩ at 27 Hz, and the rectified DC output voltage reaches 1.84 V, which shows coincidence with simulation results and is proved to be sufficient for powering LED electronics.

Ultrasound-Guided High-Intensity Focused Ultrasound for Devascularization of Uterine Fibroid: A Feasibility Study.

This study aimed to establish the feasibility of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for devascularization of uterine fibroids. Ultrasound color Doppler flow imaging (CDFI) and B-mode imaging were used to target fibroid vascularity. The vessels were covered and ablated by high-intensity focused ultrasound spots. In this study, 42 fibroids with a volume of 66.98 ± 4.00 cm3 were treated. No blood flow was detected by post-treatment CDFI in 40 fibroids. The 6-mo non-perfusion volume rate was 75.23% ± 34.77% (n = 40). The mean shrinkage in fibroid volume was 38.20% and 43.89%, respectively, at 1 and 6 mo after treatment (p < 0.001). The uterine fibroid symptom and quality of life scores were reduced by 9.43% at 1 mo and 26.66% at 6-mo after treatment (p < 0.001). No serious adverse event was observed. This study demonstrates the feasibility of USgHIFU-induced fibroid devascularization, and more studies are required for the evaluation of safety and efficacy.