Phenylacetylene-Terminated Poly(Ethylene Glycol) as Ligands for Colloidal Noble Metal Nanoparticles: a New Tool for "Grafting to" Approach.

We report a new design of polymer phenylacetylene (PA) ligands and the ligand exchange methodology for colloidal noble metal nanoparticles (NPs). PA-terminated poly(ethylene glycol) (PEG) can bind to metal NPs through acetylide (M-C≡C-R) that affords a high grafting density. The ligand-metal interaction can be switched between σ bonding and extended π backbonding by changing grafting conditions. The σ bonding of PEG-PA with NPs is strong and it can compete with other capping ligands including thiols, while the π backbonding is much weaker. The σ bonding is also demonstrated to improve the catalytic performance of Pd for ethanol oxidation and prevent surface absorption of the reaction intermediates. Those unique binding characteristics will enrich the toolbox in the control of colloidal surface chemistry and their applications using polymer ligands.

Evaluation of drug resistance for EGFR-TKIs in Lung Cancer via Multicellular lung-on-a-chip.

Drug resistance to irreversible epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is a primary factor affecting their therapeutic efficacy in human non-small cell lung cancer (NSCLC). NSCLC cells can undergo epithelial-mesenchymal transition (EMT) induced by many factors in the tumour microenvironment (TME), which plays a crucial role in tumour drug resistance. In this study, a multicellular lung-on-a-chip that can realise the cell co-culture of the human non-small cell lung cancer cell line HCC827, human foetal lung fibroblasts (HFL-1), and human umbilical vein endothelial cells (HUVECs) is prepared. The TME was simulated on the chip combined with perfusion and other factors, and the drug evaluation of osimertinib was performed to explore the drug resistance mechanism of EGFR-TKIs. In the early stages, a two-dimensional static cell co-culture was achieved by microchip, and the results showed that HFL-1 cells could be transformed into cancer-associated fibroblasts (CAFs), and HCC827 cells could undergo EMT, both of which were mediated by Interleukin-6 (IL-6). Vimentin (VIM) and Alpha Skeletal Muscle Actin (a-SMA) expression of HFL-1 was upregulated, whereas E-cadherin (E-cad) expression of HCC827 was down-regulated. Further, N-cadherin (N-cad) expression of HCC827 was upregulated. In both the static cell co-culture and multicellular lung-on-a-chip, HCC827 cells with CAFs co-culture or IL-6 treatment developed resistance to osimertinib. Further use of the IL-6 antibody inhibitor tocilizumab could reverse EGFR-TKI resistance to a certain extent. Combination therapy with tocilizumab and EGFR-TKIs may provide a novel therapeutic strategy for overcoming EGFR-TKI resistance caused by EMT in NSCLC. Furthermore, the lung-on-a-chip can simulate complex TME and can be used for evaluating tumour resistance and exploring mechanisms, with the potential to become an important tool for personalised diagnosis, treatment, and biomedical research.

Evaluating the effectiveness of dual dye combination of indocyanine green and carbon nanoparticles with parathyroid hormone test in preserving parathyroid gland during papillary thyroid cancer surgery: a single-center retrospective cohort study.

Preserving the integrity of parathyroid glands is crucial in papillary thyroid cancer (PTC) surgery to avoid hypoparathyroidism. In recent years, two novel dyes, activated carbon nanoparticles (CNP) and indocyanine green (ICG), have been utilized to assist in parathyroid gland identification. However, the use of CNP or ICG alone can result in extravasation of dye or excessive fluorescence of non-parathyroid tissue, which can affect the accuracy of surgical outcomes by yielding false negative or false positive results. Therefore, it is important to further optimize the application of these two dyes in surgery. We analyzed case files of 124 PTC patients who underwent routine total or near-total thyroidectomy with bilateral lymph node dissection in the central region at the Affiliated People's Hospital of Ningbo University from January to November 2022. The patients were randomly divided into three groups based on the type of intraoperative dye used. The CNP group (n = 38) received an intra-thyroidal injection of CNP dye. The ICG group (n = 42) used the ICG near-infrared fluorescence endoscopy system to show parathyroid fluorescence. The group that received a combined approach of ICG and CNP (n = 44) leveraged the advantages of both methods that allow for positive development of ICG and negative development of CNP to identify and preserve the parathyroid gland during operation. The parathyroid hormone detection reagent (PTH test method) was employed to verify the highly suspected parathyroid tissue in all three groups. We analyzed intraoperative data pertaining to intraoperative parathyroid identification, misexcision, number of autotransplantation, and postoperative hypoparathyroidism among the three groups. Compared with the ICG group and the CNP group, the combined group demonstrated more prominent advantages in identifying average the number of lower parathyroid glands (1.93 ± 0.26, p = 0.015), reducing the average numberrate of misexcision (0.45 ± 0.5, p = 0.004), and reducing the incidence of postoperative temporary hypothyroidism (3/44, p = 0.015). The combined use of ICG and CNP dual-dye with PTH test method appears to be more effective in both identifying and protecting parathyroid glands during PTC surgery.

Preparation and Mechanism Analysis of Stainless Steel AOD Slag Mixture Base Materials.

To promote resourceful utilization of argon oxygen decarburization (AOD) slag, this research developed a new three-ash stabilized recycled aggregate with AOD slag, cement, fly ash (FA), and recycled aggregate (RA) as raw materials. The AOD slag was adopted as an equal mass replacement for fly ash. The application of this aggregate in a road base layer was investigated in terms of its mechanical properties and mechanistic analysis. First, based on a cement: FA ratio of 1:4, 20 sets of mixed proportion schemes were designed for four kinds of cement dosage and AOD slag replacement rates (R/%). Through compaction tests and the 7-day unconfined compressive strength test, it was found that a 3% cement dosage met the engineering requirements. Then, the unconfined compressive strength test, indirect tensile strength test, compressive rebound modulus test, and expansion rate test were carried out at different age thresholds. The results showed that the mixture's strength, modulus, and expansion rate increased initially and then stabilized with age, while the strength and modulus initially increased and then decreased with increasing R. Secondly, based on X-ray diffraction (XRD) and scanning electron microscopy (SEM) used to analyze the mechanism, it was found that the strength, modulus, and expansion rate of the new material can be promoted by blending AOD slag, due to its ability to fully stimulate the hydration reaction and pozzolanic reaction of the binder. Finally, based on the strength and modulus results, R = 3% was identified as the optimal ratio, which provides a reference point for the effective application of AOD slag and RA in road base materials.

Updated prevalence of latent prostate cancer in Chinese population and comparison of biopsy results: An autopsy-based study.

Prostate cancer detected by autopsy is named latent prostate cancer. As the repertoire of clinical prostate cancer, latent cancer may better reflect the disease burden. Unlike clinical prostate specimens, which are obtained exclusively from biopsy-positive cases, prostate specimens obtained through autopsy provide information on biopsy-negative cases, helping calculate the true sensitivity of prostate biopsy. From 2014 to 2021, we collected autopsy specimens of the prostate from body donors in China and performed transperineal and transrectal biopsies on specimens before step-sectioning and pathological measurements. We found that the crude prevalence of latent prostate cancer in middle-aged and elderly men was 35.1% (81/231), which was higher than previous estimates for Chinese populations. The overall per-patient sensitivities of transperineal and transrectal biopsies were not significantly different (33.3% vs. 32.1%, p = 0.82), but the two approaches differed in preferential sampling area along the proximal-distal axis of the prostate. Transperineal biopsy had a higher sensitivity for detecting clinically significant lesions in the distal third (34.7% vs. 16.3%, p = 0.02) and distal half (30.6% vs. 18.1%, p = 0.04), while transrectal biopsy had a higher sensitivity for lesions in the proximal half (25.0% vs. 13.9%, p = 0.046). Both transperineal and transrectal methods of biopsy missed most small lesions (<0.1 mL) and 35.3% (6/17) of large lesions (>0.5 mL). In conclusion, the prevalence of latent prostate cancer in China has increased over the past 2 decades. Systematic transperineal and transrectal methods of biopsy had comparable sensitivities but had different preferential sampling areas. Both approaches miss one-third of large lesions.

Study on the Design and Performance of a Glove Based on the FBG Array for Hand Posture Sensing.

This study introduces a new wearable fiber-optic sensor glove. The glove utilizes a flexible material, polydimethylsiloxane (PDMS), and a silicone tube to encapsulate fiber Bragg gratings (FBGs). It is employed to enable the self-perception of hand posture, gesture recognition, and the prediction of grasping objects. The investigation employs the Support Vector Machine (SVM) approach for predicting grasping objects. The proposed fiber-optic sensor glove can concurrently monitor the motion of 14 hand joints comprising 5 metacarpophalangeal joints (MCP), 5 proximal interphalangeal joints (PIP), and 4 distal interphalangeal joints (DIP). To expand the measurement range of the sensors, a sinusoidal layout incorporates the FBG array into the glove. The experimental results indicate that the wearable sensing glove can track finger flexion within a range of 0° to 100°, with a modest minimum measurement error (Error) of 0.176° and a minimum standard deviation (SD) of 0.685°. Notably, the glove accurately detects hand gestures in real-time and even forecasts grasping actions. The fiber-optic smart glove technology proposed herein holds promising potential for industrial applications, including object grasping, 3D displays via virtual reality, and human-computer interaction.

Antioxidant Nanoparticles Restore Cisplatin-Induced Male Fertility Defects by Promoting MDC1-53bp1-Associated Non-Homologous DNA Repair Mechanism and Sperm Intracellular Calcium Influx.

Introduction: Cisplatin, a commonly used anticancer compound, exhibits severe off-target organ toxicity. Due to its wide application in cancer treatment, the reduction of its damage to normal tissue is an imminent clinical need. Cisplatin-induced testicular oxidative stress and damage lead to male sub- or infertility. Despite earlier studies showing that the natural polyphenol extracts honokiol serve as the free radical scavenger that reduces the accumulation of intracellular free radicals, whether honokiol exhibits direct effects on the testis and sperm is unclear. Thus, the aim of the current study is to investigate the direct effects of honokiol on testicular recovery and sperm physiology. Methods: We encapsulated this polyphenol antioxidation compound into liposome-based nanoparticles (nHNK) and gave intraperitoneally to mice at a dosage of 5 mg/kg body mass every other day for consecutive 6 weeks. Results: We showed that nHNK promotes MDC1-53bp1-associated non-homologous DNA double-strand break repair signaling pathway that minimizes cisplatin-induced DNA damage. This positive effect restores spermatogenesis and allows the restructuring of the multi-spermatogenic layers in the testis. By reducing mitochondrial oxidative damage, nHNK also protects sperm mitochondrial structure and maintains both testicular and sperm ATP production. By a yet-to-identify mechanism, nHNK restores sperm calcium influx at the sperm midpiece and tail, which is essential for sperm hypermotility and their interaction with the oocyte. Discussion: Taken together, the nanoparticulated antioxidant counteracts cisplatin-induced male fertility defects and benefits patients undertaking cisplatin-based chemotherapy. These data may allow the reintroduction of cisplatin for systemic applications in patients at clinics with reduced testicular toxicity.

Up-to-Date Imaging and Diagnostic Techniques for Prostate Cancer: A Literature Review.

Prostate cancer (PCa) faces great challenges in early diagnosis, which often leads not only to unnecessary, invasive procedures, but to over-diagnosis and treatment as well, thus highlighting the need for modern PCa diagnostic techniques. The review aims to provide an up-to-date summary of chronologically existing diagnostic approaches for PCa, as well as their potential to improve clinically significant PCa (csPCa) diagnosis and to reduce the proliferation and monitoring of PCa. Our review demonstrates the primary outcomes of the most significant studies and makes comparisons across the diagnostic efficacies of different PCa tests. Since prostate biopsy, the current mainstream PCa diagnosis, is an invasive procedure with a high risk of post-biopsy complications, it is vital we dig out specific, sensitive, and accurate diagnostic approaches in PCa and conduct more studies with milestone findings and comparable sample sizes to validate and corroborate the findings.

Faster Return to Daily Activities and Better Pain Control: A Prospective Study of Enhanced Recovery After Surgery Protocol in Breast Augmentation.

BACKGROUND: Enhanced recovery after surgery (ERAS) has been proven to decrease the amount of opioid use and reduce postoperative pain for a variety of surgeries, including breast reconstruction. However, data on ERAS in breast augmentation is lacking. OBJECTIVES: This study aims to investigate the effectiveness and safety of ERAS for breast augmentation. METHODS: A standardized ERAS protocol was established with full consideration of all aspects of perioperative care. Patients undergoing implant-based breast augmentation were prospectively recruited between December 2020 and January 2023, and assigned to either the ERAS or non-ERAS group randomly. The primary outcome was the activity of daily living after surgery. The secondary was postoperative pain and other outcomes included time to freely elevation, vomiting frequency, the use of analgesics, and complications. RESULTS: A total of 122 patients were included, with 70 in the ERAS group and 52 in the non-ERAS group. Compared to non-ERAS patients, ERAS patients had a shorter time to freely elevation of upper limbs (2.3 d vs. 5.5 d, P < 0.001). For ERAS patients, the pain scores were significantly lower on postoperative days 1 to 3, the activity of daily living index was significantly higher on postoperative days 1 to 3 and the opioids consumption was decreased (7.1 mg vs. 46.2 mg, P = 0.018). No difference was observed in complication and hospital costs between the two groups. CONCLUSION: The ERAS protocol significantly reduced postoperative pain and the use of opioids and promoted a return to daily activities without increasing complications in breast augmentation. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A magnetic skyrmion diode based on potential well inducting effect.

Magnetic skyrmions have great potential in the application of spintronic devices due to their stable topologically protected spin configuration. To meet the needs of spintronic device design, it is necessary to manipulate the movement of the magnetic skyrmions. Here we propose a skyrmion diode based on potential well induced skyrmion motion through theoretical calculations. The potential well is generated by the voltage-controlled magnetic anisotropy (VCMA) gradient. By utilizing the induction of the potential well as well as the skyrmion Hall effect (SkHE), the velocity and trajectory of the skyrmions can be controlled and the forward pass and reverse cutoff functions of diode-like devices have been realized. Furthermore, we report the dynamics of current-driven skyrmions in a racetrack with locally applied VCMA. Under the influence of the SkHE, the difference in dynamic behavior between forward and reverse motion of the skyrmions is obvious, and the potential well can produce different pinning, depinning and annihilating effects on forward and reverse moving skyrmions. Our results can be beneficial for the design and development of magnetic skyrmion diodes.

Dengue transmission dynamics prediction by combining metapopulation networks and Kalman filter algorithm.

Predicting the specific magnitude and the temporal peak of the epidemic of individual local outbreaks is critical for infectious disease control. Previous studies have indicated that significant differences in spatial transmission and epidemic magnitude of dengue were influenced by multiple factors, such as mosquito population density, climatic conditions, and population movement patterns. However, there is a lack of studies that combine the above factors to explain their complex nonlinear relationships in dengue transmission and generate accurate predictions. Therefore, to study the complex spatial diffusion of dengue, this research combined the above factors and developed a network model for spatiotemporal transmission prediction of dengue fever using metapopulation networks based on human mobility. For improving the prediction accuracy of the epidemic model, the ensemble adjusted Kalman filter (EAKF), a data assimilation algorithm, was used to iteratively assimilate the observed case data and adjust the model and parameters. Our study demonstrated that the metapopulation network-EAKF system provided accurate predictions for city-level dengue transmission trajectories in retrospective forecasts of 12 cities in Guangdong province, China. Specifically, the system accurately predicts local dengue outbreak magnitude and the temporal peak of the epidemic up to 10 wk in advance. In addition, the system predicted the peak time, peak intensity, and total number of dengue cases more accurately than isolated city-specific forecasts. The general metapopulation assimilation framework presented in our study provides a methodological foundation for establishing an accurate system with finer temporal and spatial resolution for retrospectively forecasting the magnitude and temporal peak of dengue fever outbreaks. These forecasts based on the proposed method can be interoperated to better support intervention decisions and inform the public of potential risks of disease transmission.

Study of the Metabolite Changes in Ganoderma lucidum under Pineapple Leaf Residue Stress via LC-MS/MS Coupled with a Non-Targeted Metabolomics Approach.

The effects of fermentation metabolites of G. lucidum under different pineapple leaf residue additions were separated and identified using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The mass spectra showed that the metabolites had good response values only in the positive ion mode, and 3019 metabolites with significant differences, mainly distributed in 95 metabolic pathways, were identified. The multivariate analyses, including the principal component analysis (PCA), orthogonal least squares discriminant analysis (OPLS-DA), and volcano plots (VP), revealed that the G. lucidum metabolites exhibited significant differences (p < 0.05) and were well clustered under various pineapple leaf residue additions, featuring 494-545 upregulated and 998-1043 downregulated metabolites. The differential metabolic pathway analysis proved that two metabolic pathways related to the biosynthesis of amino acids and ABC transporters were particularly significant under the addition of pineapple leaf residue, where amino acids such as histidine and lysine were upregulated in contrast to downregulated tyrosine, valine, L-alanine, and L-asparagine. These study results are considered instrumental in substantiating the application of pineapple leaf residue in the cultivation of G. lucidum and improving its utilization rate and added value.

Clear cell renal cell carcinoma molecular variations in non-Hispanic White and Hispanic patients.

BACKGROUND: The United States is becoming increasingly diverse, but few molecular studies have assessed the progression of clear cell renal cell carcinoma (ccRCC) in diverse patient populations. This study examined ccRCC molecular variations in non-Hispanic White (NHW) and Hispanic patients and their effect on the association of gene expression with high-grade (Grade 3 or 4) ccRCC and overall mortality. METHODS: A total of 156 patients were included in VHL sequencing and/or TempO-Seq analysis. DESeq2 was used to identify the genes associated with high-grade ccRCC. Logistic regression analysis was performed to assess whether race and ethnicity was associated with high/moderate impact VHL somatic mutations and the ccA/ccB subtype. Cox regression analysis was performed to assess association of molecular subtype and gene expression with overall mortality. RESULTS: NHWs had moderate or high impact mutations in the VHL gene at a higher frequency than Hispanics (40.2% vs. 27.4%), while Hispanics had a higher frequency of the ccA subtype than NHWs (61.9% vs. 45.8%). ccA was more common in patients with BMI≥35 (65.2%) than in those with BMI < 25 (45.0%). There were 11 differentially expressed genes between high- and low-grade tumors. The Haptoglobin (HP) gene was most significantly overexpressed in high- compared to low-grade ccRCC in all samples (p-adj = 1.7 × 10-12 ). When stratified by subtype, the 11 genes were significantly differentially expressed in the ccB subtype, but none of them were significant after adjusting for multiple testing in ccA. Finally, patients with the ccB subtype had a significantly increased risk of overall mortality (HR 4.87; p = 0.01) compared to patients with ccA, and patients with high HP expression and ccB, had a significantly increased risk of mortality compared to those with low HP expression and ccA (HR 6.45, p = 0.04). CONCLUSION: This study reports ccRCC molecular variations in Hispanic patients who were previously underrepresented.

Genome-Wide Association Study of Metachronous Colorectal Adenoma Risk among Participants in the Selenium Trial.

Genetic variants related to colorectal adenoma may help identify those who are at highest risk of colorectal cancer development or illuminate potential chemopreventive strategies. The purpose of this genome-wide association study was to identify genetic variants that are associated with risk of developing a metachronous colorectal adenoma among 1,215 study participants of European descent from the Selenium Trial. Associations of variants were assessed with logistic regression analyses and validated in an independent case-control study population of 1,491 participants from the Colorectal Cancer Study of Austria (CORSA). No statistically significant genome-wide associations between any variant and metachronous adenoma were identified after correction for multiple comparisons. However, an intron variant of FAT3 gene, rs61901554, showed a suggestive association (P = 1.10 × 10-6) and was associated with advanced adenomas in CORSA (P = 0.04). Two intronic variants, rs12728998 and rs6699944 in NLRP3 were also observed to have suggestive associations with metachronous lesions (P = 2.00 × 10-6) in the Selenium Trial and were associated with advanced adenoma in CORSA (P = 0.03). Our results provide new areas of investigation for the genetic basis of the development of metachronous colorectal adenoma and support a role for FAT3 involvement in the Wnt/ß-catenin pathway leading to colorectal neoplasia.Trial Registration number: NCT00078897 (ClinicalTrials.gov).

Experiment on Compressive Properties and Microscopic Analysis of Sea Sand Geopolymer-Based Recycled Concrete.

For marine and coastal engineering, construction resources have become scarce due to a limited local supply. Sea sand geopolymer-based recycled concrete (SSGRC) is an innovative cementitious material known for its eco-friendly benefits and corrosion resistance. This study explores the mechanical properties of SSGRC. The influences of the replacement rate of mineral slag, alkali activator concentrations, fine aggregate types, and curing ages on the compression strength of SSGRC were studied. The failure mechanism was analyzed using the failure patterns and compressive stress-strain curves. The results show that sea sand had a positive effect on geopolymer-based material. The SSGRC reached peak strength with an alkali activator concentration of 10 mol/L and a mineral slag replacement rate of 60%. The maximum stress and strain increased with an increasing curing age. The ratios of strength to the peak value were 55% and 85% after 1 day and 7 days, respectively. Using SEM, in the last hydration stage, the C-(A)-S-H gel was formed with a dense microstructure, and the geopolymer exhibited a favorable bonding performance. The constitutive models describing the complete stress-strain relationship under compression were developed.

Experimental Study on Vibratory Compaction Behavior of Tunneling Rock Wastes Used as Unbound Permeable Aggregate Base Materials.

The tunneling rock wastes (TRW) have been increasingly generated and stockpiled in massive quantities. Recycling them for use as unbound granular pavement base/subbase materials has become an alternative featuring low carbon emission and sustainability. However, the field compaction of such large-size, open-graded materials remains challenging, thus affecting post-construction deformation and long-term stability of such pavement base/subbase layers. This study conducted a series of proctor compaction and new plate vibratory compaction tests to analyze the compaction characteristics of such TRW materials. A total of six different open gradations were designed from particle packing theory. In addition, the effects of gradation and compaction methods on the compaction characteristics, particle breakage of TRW materials, and the optimal combination of vibratory parameters were investigated by normalizing the curves of achieved dry density versus degree of saturation for various combinations of gradations, compaction methods, and compaction energy levels. The post-compaction characteristics of interparticle contact, pore structure, and particle breakage were analyzed from the X-ray computed topography (XCT) scanning results of TRW specimens with different gradations. The findings showed that the gravel-to-sand ratio (G/S) based gradation design method can effectively differentiate distinct types of particle packing structures. There exists an optimal G/S range that could potentially result in the highest maximum dry density, the lowest particle breakage, and the best pore structure of compacted unbound permeable aggregate base (UPAB) materials. The achieved dry density (ρd) of UPAB materials subjected to vibratory plate compaction exhibited three distinct phases with compaction time, from which the optimal excitation frequency range was found to be 25-27 Hz and the optimal combination of vibratory parameters were determined. The normalized compaction curves of degree of saturation versus achieved dry density were found insensitive to changes in material gradations, compaction methods and energy levels, thus allowing for a more accurate evaluation and control of field compaction quality.

Expression of genes related to antioxidation, immunity, and heat stress in Gambusia affinis exposed to the heavy metals Cu and Zn.

Water pollution is an increasingly serious problem. Here, Cu and Zn ions were used as stress factors, and G. affinis served as a test organism. Fluorescence quantitative PCR was used to detect changes in the expression of antioxidant genes (SOD, GST, CAT), heat stress genes (Hsp70, Hsp90, Hspd1, Hsc70), and immune system-related genes (IL-1ß, IL-8) in G. affinis exposed to Cu and Zn ions over time. To explore the toxic effects of Cu and Zn on G. affinis. The results showed that the 48 h LC50 concentrations of the heavy metals Cu and Zn to G. affinis were 0.17 mg/L and 44.67 mg/L, respectively. Within 48 h, with prolonged Cu exposure, the relative expression levels of the Hsp70, Hsp90, Hspd1, Hsc70, SOD, GST, and CAT genes in the gill tissue first showed a significant increase and then gradually decreased. Gene expression peaked between 9 and 36 h. The relative expression levels of SOD and GST genes in liver tissue showed a gradual decline. Within 48 h, with prolonged Zn exposure, the expression levels of SOD, CAT, and GST genes in G. affinis first increased and then fell before finally rising. The expression levels of IL-1ß and IL-8 mRNA showed varying degrees of upward trends, and the expression of IL-8 was the highest for all gill tissue. To sum up, Cu and Zn have strong toxic effects on G. affinis, which makes it possible to use G. affinis as indicator organisms for aquatic environmental pollution.

Fabrication of an Au-doped Cu/Fe oxide-polymer core-shell nanoreactor with chemodynamic and photodynamic dual effects as potential cancer therapeutic agents.

Nanoparticles are widely used in biomedical applications and cancer treatments due to their minute scale, multi-function, and long retention time. Among the various nanoparticles, the unique optical property derived from the localized surface plasmon resonance effect of metallic nanoparticles is a primary reason that metallic nanoparticles are researched and applied. Copper and Iron nanoparticles have the potential to generate hydroxyl radicals in excess H2O2 via Fenton or Fenton-like reactions. On the other hand, gold nanoparticles equipped with a photosensitizer can transfer the energy of photons to chemical energy and enhance the production of singlet oxygen, which is suitable for cancer treatment. With the actions of these two reactive oxygen species in the tumor microenvironment, cell apoptosis can further be induced. In this work, we first synthesized dual metal nanoparticles with poly[styrene-alt-(maleic acid, sodium salt)(Cu ferrite oxide-polymer) by a simple one-step hydrothermal reduction reaction. Then, gold(III) was reduced and doped into the structure, which formed a triple metal structure, Au-doped Cu ferrite nanoparticles (Au/Cu ferrite oxide-polymer NPs). The metal ratio of the product could be controlled by manipulating the Fe/Cu ratio of reactants and the sequence of addition of reactants. The core-shell structure was verified by transmission electron microscopy. Moreover, the hydroxyl radical and singlet oxygen generation ability of Au/Cu ferrite oxide-polymer was proved. The chemodynamic and photodynamic effect was measured, and the in vitro ROS generation was observed. Furthermore, the behavior of endocytosis by cancer cells could be controlled by the magnetic field. The result indicated that Au/Cu ferrite oxide-polymer core-shell nanoreactor is a potential agent for chemodynamic/photodynamic synergetic therapy.

Development of Human Pituitary Neuroendocrine Tumor Organoids to Facilitate Effective Targeted Treatments of Cushing's Disease.

(1) Background: Cushing's disease (CD) is a serious endocrine disorder caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary neuroendocrine tumor (PitNET) that stimulates the adrenal glands to overproduce cortisol. Chronic exposure to excess cortisol has detrimental effects on health, including increased stroke rates, diabetes, obesity, cognitive impairment, anxiety, depression, and death. The first-line treatment for CD is pituitary surgery. Current surgical remission rates reported in only 56% of patients depending on several criteria. The lack of specificity, poor tolerability, and low efficacy of the subsequent second-line medical therapies make CD a medical therapeutic challenge. One major limitation that hinders the development of specific medical therapies is the lack of relevant human model systems that recapitulate the cellular composition of PitNET microenvironment. (2) Methods: human pituitary tumor tissue was harvested during transsphenoidal surgery from CD patients to generate organoids (hPITOs). (3) Results: hPITOs generated from corticotroph, lactotroph, gonadotroph, and somatotroph tumors exhibited morphological diversity among the organoid lines between individual patients and amongst subtypes. The similarity in cell lineages between the organoid line and the patient's tumor was validated by comparing the neuropathology report to the expression pattern of PitNET specific markers, using spectral flow cytometry and exome sequencing. A high-throughput drug screen demonstrated patient-specific drug responses of hPITOs amongst each tumor subtype. Generation of induced pluripotent stem cells (iPSCs) from a CD patient carrying germline mutation CDH23 exhibited dysregulated cell lineage commitment. (4) Conclusions: The human pituitary neuroendocrine tumor organoids represent a novel approach in how we model complex pathologies in CD patients, which will enable effective personalized medicine for these patients.