Dosimetric Correlation of Acute Radiation Dermatitis in Patients With Breast Cancer Undergoing Hypofractionated Proton Beam Therapy Using Pencil Beam Scanning.

PURPOSE: Pencil-beam scanning (PBS) is a modern delivery technique used in proton beam therapy (PBT) to reduce normal tissue reactions. No dosimetric correlation between dermatitis and PBS has been reported for breast cancer. The current study aimed to investigate the factors associated with grade 2 or higher dermatitis in patients with breast cancer undergoing PBT using PBS. METHODS: The medical data of 42 patients with breast cancer who underwent adjuvant radiotherapy between December 2019 and September 2023 were reviewed. All patients received hypofractionated radiotherapy (HFRT), either 26 Gy (relative biological effectiveness [RBE])/five fractions or 40.05 or 43.5 Gy (RBE)/15 fractions, for the whole breast/chest wall with or without nodal irradiation. The duration of acute radiation dermatitis was defined as within 90 days from the start of radiotherapy. The Kaplan-Meier method and Cox proportional hazards model were used for univariate and multivariate analyses of the actuarial rates of grade 2-3 dermatitis. RESULTS: Twenty-two (52.4%) and 20 (47.6%) patients were diagnosed with grade 1 and 2 dermatitis, respectively. Multivariate analysis revealed a clinical target volume (CTV) ≥ of 320 cc (p = 0.035) and a skin dose of D10cc ≥ 38.3 Gy (RBE) (p = 0.009) as independent factors of grade 2 dermatitis. The 10-week cumulative grade 2 dermatitis rates were 88.2%, 39.4%, and 8.3% (p < 0.001) for patients with both high, either high, and neither high CTV and D10cc, respectively. CONCLUSION: To the best of our knowledge, this is the first study on dosimetric correlations for dermatitis in patients with breast cancer who underwent hypofractionated PBT using PBS. In the era of HFRT, skin dose modulation using PBS may reduce the incidence of dermatitis.

The risk of free flap revision and subsequent medical costs in patients with hypopharyngeal cancer.

BACKGROUND: Few studies have examined the preoperative risks and healthcare costs related to free flap revision in hypopharyngeal cancer (HPC) patients. METHODS: A 20-year retrospective case-control study was conducted using the Chang Gung Research Database, focusing on HPC patients who underwent tumor excision and free flap reconstruction from January 1, 2001, to December 31, 2019. The impacts of clinical variables on the need for re-exploration due to free flap complications were assessed using logistic regression. The direct and indirect effects of these complications on medical costs were evaluated by causal mediation analysis. RESULTS: Among 348 patients studied, 43 (12.4%) developed complications requiring re-exploration. Lower preoperative albumin levels significantly increased the risk of complications (OR 2.45, 95% CI 1.12-5.35), especially in older and previously irradiated patients. Causal mediation analysis revealed that these complications explained 11.4% of the effect on increased hospitalization costs, after controlling for confounders. CONCLUSIONS: Lower preoperative albumin levels in HPC patients are associated with a higher risk of microvascular free flap complications and elevated healthcare costs, underscoring the need for enhanced nutritional support before surgery in this population.

Short-term supplementation with uncoated and encapsulated Enterococcus faecium affected growth performance, gut microbiome and intestinal barrier integrity in broiler chickens.

Enterococcus faecium (E. faecium) is an alternative to antibiotics, while the probiotic effect of short-term application in mature broiler chickens remains unclear. In the current study, 48 Arbor Acres male broilers were chosen to investigate the effects of E. faecium on growth performance, the gut microbiome and intestinal health during the finishing period. Forty-eight birds were randomly allocated to 4 treatment groups that were fed a corn-soybean meal basal diet (Con), a basal diet supplemented with 1 g/kg amoxicillin (ABX), 5×106 CFU/g encapsulated E. faecium (cEF), or 5×106 CFU/g uncoated E. faecium (EF) from d 33 to 42. The results showed that 10 d of antibiotic treatment decreased the growth performance of the broilers (P < 0.05). The feed conversion ratio of the cEF and EF groups were lower than that of the Con group by 0.13 and 0.07, respectively (P > 0.05). The abundance of viable ileal and cecal E. faecium in the cEF group was greater than that in the EF group (P < 0.05), and both groups were markedly greater than those in the Con and ABX groups (P < 0.05). The ABX treatment decreased the Shannon and Chao1 indices of the cecal microbiota, while the dietary E. faecium treatment resulted in significant differences in the ß diversity of the ileal and cecal microbiota (P < 0.05). Mantel correlation revealed that the ileal microbiota at the genus level was significantly correlated with the growth performance of broilers, with Lactobacillus, Bacillus and Escherichia-Shigella showing positive and strong correlations (P < 0.05). In the ileum, the crypt depth was lower in the cEF group than in the Con group, but the villi height-to-crypt depth ratio was greater in the cEF group than in the other groups (P = 0.037). However, the expression of the ZO-2 and Occludin genes was downregulated in the E. faecium-fed birds (P < 0.05). In the cecum, the acetate, butyrate and total SCFA levels were greater in the EF group (P < 0.05), while the propionate, isobutyrate and isovalerate levels were lower in the ABX group (P < 0.05). In summary, 10 d of dietary supplementation with E. faecium markedly increased colonization in mature broilers and potentially improved growth performance by modulating the ileal microbiota. Encapsulation techniques could enable a slow release of E. faecium in the intestine, thereby reducing the negative impacts of rapid expansion of E. faecium on the intestinal epithelium.

CCT6A facilitates lung adenocarcinoma progression and glycolysis via STAT1/HK2 axis.

BACKGROUND: Chaperonin Containing TCP1 Subunit 6 A (CCT6A) is a prominent protein involved in the folding and stabilization of newly synthesized proteins. However, its roles and underlying mechanisms in lung adenocarcinoma (LUAD), one of the most aggressive cancers, remain elusive. METHODS: Our study utilized in vitro cell phenotype experiments to assess CCT6A's impact on the proliferation and invasion capabilities of LUAD cell lines. To delve into CCT6A's intrinsic mechanisms affecting glycolysis and proliferation in lung adenocarcinoma, we employed transcriptomic sequencing and liquid chromatography-mass spectrometry analysis. Co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (CHIP) assays were also conducted to substantiate the mechanism. RESULTS: CCT6A was found to be significantly overexpressed in LUAD and associated with a poorer prognosis. The silencing of CCT6A inhibited the proliferation and migration of LUAD cells and elevated apoptosis rates. Mechanistically, CCT6A interacted with STAT1 protein, forming a complex that enhances the stability of STAT1 by protecting it from ubiquitin-mediated degradation. This, in turn, facilitated the transcription of hexokinase 2 (HK2), a critical enzyme in aerobic glycolysis, thereby stimulating LUAD's aerobic glycolysis and progression. CONCLUSION: Our findings reveal that the CCT6A/STAT1/HK2 axis orchestrated a reprogramming of glucose metabolism and thus promoted LUAD progression. These insights position CCT6A as a promising candidate for therapeutic intervention in LUAD treatment.

ZNF574 is a Quality Control Factor For Defective Ribosome Biogenesis Intermediates.

Eukaryotic ribosome assembly is an intricate process that involves four ribosomal RNAs, 80 ribosomal proteins, and over 200 biogenesis factors that take part in numerous interdependent steps. This complexity creates a large genetic space in which pathogenic mutations can occur. Dead-end ribosome intermediates that result from biogenesis errors are rapidly degraded, affirming the existence of quality control pathway(s) that monitor ribosome assembly. However, the factors that differentiate between on-path and dead-end intermediates are unknown. We engineered a system to perturb ribosome assembly in human cells and discovered that faulty ribosomes are degraded via the ubiquitin proteasome system. We identified ZNF574 as a key component of a novel quality control pathway, which we term the Ribosome Assembly Surveillance Pathway (RASP). Loss of ZNF574 results in the accumulation of faulty biogenesis intermediates that interfere with global ribosome production, further emphasizing the role of RASP in protein homeostasis and cellular health.

Comparative Analysis of Oncologic Outcomes in Patients with Squamous Cell Carcinoma of the Uterine Cervix with High-Risk Features for Para-Aortic Recurrence: Prophylactic Extended-Field versus Pelvic Chemoradiotherapy.

Purpose: To compare the oncologic outcomes of prophylactic extended-field radiation therapy (EFRT) and whole pelvic radiation therapy (WPRT) in cervical patients at high risk of para-aortic lymph node (PALN) recurrence. Patients and Methods: From July 1999 to May 2022, a total of 115 patients with cervical cancer and high-risk features of PALN recurrence based on tumor markers, positive LNs and extensive parametrial invasion were retrospectively analyzed. All patients had received EFRT or WPRT at a dose of 39.6-45 Gy and concurrent chemotherapy. In EFRT, coverage was extended to include the para-aortic region below the level of the left renal vein or T12. Results: Twenty-eight and 87 patients underwent EFRT and WPRT, respectively. For patients who survived, the median follow-up time was 60.8 months (range 9.2-131.6 months) in the EFRT group and 115.9 months (range 16.9-212.1 months) in the WPRT group. The 5-year overall survival (OS) and pelvic, extrapelvic and PALN recurrence rates were 87.7% vs 60.8% (p=0.019), 10.9% vs 25.3% (p=0.119), 18.1% vs 45.8% (p=0.011), and 0% vs 30.4% (p=0.005), respectively, between the EFRT and WPRT groups. Multivariate analysis revealed that EFRT and 2018 FIGO stage IV disease status were significant predictors of OS and extrapelvic recurrence. Conclusion: Compared to WPRT, EFRT significantly improved OS and reduced extrapelvic and PALN recurrence in patients with cervical cancer with high-risk recurrence features.

RBM10 C761Y mutation induced oncogenic ASPM isoforms and regulated ß-catenin signaling in cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma (CCA) comprises a heterogeneous group of biliary tract cancer. Our previous CCA mutation pattern study focused on genes in the post-transcription modification process, among which the alternative splicing factor RBM10 captured our attention. However, the roles of RBM10 wild type and mutations in CCA remain unclear. METHODS: RBM10 mutation spectrum in CCA was clarified using our initial data and other CCA genomic datasets from domestic and international sources. Real-time PCR and tissue microarray were used to detect RBM10 clinical association. Function assays were conducted to investigate the effects of RBM10 wild type and mutations on CCA. RNA sequencing was to investigate the changes in alternative splicing events in the mutation group compared to the wild-type group. Minigene splicing reporter and interaction assays were performed to elucidate the mechanism of mutation influence on alternative splicing events. RESULTS: RBM10 mutations were more common in Chinese CCA populations and exhibited more protein truncation variants. RBM10 exerted a tumor suppressive effect in CCA and correlated with favorable prognosis of CCA patients. The overexpression of wild-type RBM10 enhanced the ASPM exon18 exon skipping event interacting with SRSF2. The C761Y mutation in the C2H2-type zinc finger domain impaired its interaction with SRSF2, resulting in a loss-of-function mutation. Elevated ASPM203 stabilized DVL2 and enhanced ß-catenin signaling, which promoted CCA progression. CONCLUSIONS: Our results showed that RBM10C761Y-modulated ASPM203 promoted CCA progression in a Wnt/ß-catenin signaling-dependent manner. This study may enhance the understanding of the regulatory mechanisms that link mutation-altering splicing variants to CCA.

Guest Acceptors with Lower Electrostatic Potential in Ternary Organic Solar Cells for Minimizing Voltage Losses.

The ternary strategy, in which one guest component is introduced into one host binary system, is considered to be one of the most effective ways to realize high-efficiency organic solar cells (OSCs). To date, there is no efficient method to predict the effectiveness of guest components in ternary OSCs. Herein, three guest compositions (i.e., ANF-1, ANF-2 and ANF-3) with different electrostatic potential (ESP) are designed and synthesized by modulating the electron-withdrawing ability of the terminal groups through density functional theory simulations. The effects of the introduction of guest component into the host system (D18:N3) on the photovoltaic properties are investigated. The theoretical and experimental studies provide a key rule for guest acceptor in ternary OSCs to improve the open-circuit voltage, that is, the larger ESP difference between the guest and host acceptor, the stronger the intermolecular interactions and the higher the miscibility, which improves the luminescent efficiency of the blend film and the electroluminescence quantum yield (EQEEL) of the device by reducing the aggregation-caused-quenching, thereby effectively decreasing the non-radiative voltage loss of ternary OSCs. This work will greatly contribute to the development of highly efficient guest components, thereby promoting the rapid breakthrough of the 20% efficiency bottleneck for single-junction OSCs.

Dietary crude protein time-dependently modulates the bacterial community and metabolites and changes dietary nutrient efficiency in growing pigs.

The reduced nutrient digestibility of low-protein (LP) diets has been shown to be caused by the weakened fermentative capacity of the post-gut flora. The dynamic regulation of dietary protein contents on post-gut microbial population and fermentative metabolism is unclear. Twelve growing barrows (19.9 ± 0.8 kg) fitted with a T-cannula at the blind end of the cecum were randomly administered a high-protein (HP, 21.5% crude protein [CP]) diet or an LP (15.5% CP) diet for 28 d. The cecal content and feces were collected at d 1, 14, and 28 of the experiment for microflora structures and metabolite concentrations analysis. The nutrient digestibility coefficient and plasma biochemical parameters were also determined. Compared with the HP treatment, the LP treatment showed decreased plasma urea nitrogen concentration and apparent total tract digestibility of dry matter, gross energy, and CP (P < 0.01). In addition, urinary nitrogen losses, total nitrogen losses, and daily nitrogen retention in the LP treatment were lower than those in the HP treatment (P < 0.01), and the nitrogen retention-to-nitrogen intake ratio in the LP treatment was increased (P < 0.01). The HP group showed increased cecal total short-chain fatty acids (SCFA) concentration and fecal propionate, butyrate, and total SCFA concentrations (P < 0.05) on d 14 and 28, which may be mainly related to the elevated abundance of SCFA-producing bacteria, such as Ruminococcus, Lactobacillus, and Prevotella (P < 0.05). Probiotics, such as Bifidobacterium, Bacteroidales S24-7, and Rikenella, enriched in the LP treatment possibly contributed to reduced plasma endotoxin content. The differences in the abundances of almost all the above-mentioned flora appeared on d 28 but not d 14. Likewise, differences in the Simpson and Shannon indices and clustering patterns of the microbiota between treatments were also only observed on d 28. To sum up, in a time-dependent manner, the LP diet increased probiotics with gut-improving functions and decreased SCFA-producing bacteria, which may cause enhanced intestine health and reduced nutrient digestibility.

A Joint Model Based on Post-Treatment Longitudinal Prognostic Nutritional Index to Predict Survival in Nasopharyngeal Carcinoma.

BACKGROUND: a low PNI in patients with NPC is linked to poor survival, but prior studies have focused on single-timepoint measurements. Our study aims to employ joint modeling to analyze longitudinal PNI data from each routine visit, exploring its relationship with overall survival. METHODS: In this retrospective study using data from the Chang Gung Research Database (2007-2019), we enrolled patients with NPC undergoing curative treatment. We analyzed the correlation between patient characteristics, including the PNI, and overall survival. A joint model combining a longitudinal sub-model with a time-to-event sub-model was used to further evaluate the prognostic value of longitudinal PNI. RESULTS: A total of 2332 patient were enrolled for the analysis. Separate survival analyses showed that longitudinal PNI was an independent indicator of a reduced mortality risk (adjusted HR 0.813; 95% CI, 0.805 to 0.821). Joint modeling confirmed longitudinal PNI as a consistent predictor of survival (HR 0.864; 95% CI, 0.850 to 0.879). An ROC analysis revealed that a PNI below 38.1 significantly increased the risk of 90-day mortality, with 90.0% sensitivity and 89.6% specificity. CONCLUSIONS: Longitudinal PNI data independently predicted the overall survival in patients with NPC, significantly forecasting 90-day survival outcomes. We recommend routine PNI assessments during each clinic visit for these patients.

Quality of life in patients with nasopharyngeal carcinoma receiving IMRT vs IMPT: a multicenter prospective longitudinal study.

PURPOSE: Nasopharyngeal carcinoma (NPC) patients may experience symptom distress and depression during and after radiation therapy, which negatively impacts quality of life (QOL). We sought to identify trajectories of symptom distress, depression, social support, and QOL in patients with NPC receiving intensity-modulated radiation therapy (IMRT) vs intensity-modulated proton therapy (IMPT). METHODS: A multicenter prospective longitudinal study recruited NPC patients from two leading medical centers in Taiwan. The 121 NPC patients were followed from before RT (T0), at 4 weeks after beginning RT (T1), at 6 weeks of RT or the end of treatment (T2), and at 4 weeks post-RT (T3). Generalized estimating equation analysis was used to identify the factors related to QOL. RESULTS: Patients' symptom distress and depression increased from T0, peaked at T2, and decreased at T3. Physical-QOL and psychosocial-QOL decreased from T0 to T2, then increased by T3. Patients who had early-stage cancer, received a lower RT dose, had less symptom distress, and had less depression were more likely to have better QOL. Greater physical-QOL was associated with IMPT receipt, higher education level, early cancer stage, lower radiation dose, less symptom distress, and less depression. Patients who had good physical performance, received a lower radiation dose, had less symptom distress, and had less depression were more likely to have better psychosocial-QOL. CONCLUSION: Radiation dose, symptom distress, and depression were the most important factors affecting QOL in patients with NPC. Understanding the factors associated with the trajectory of QOL can guide care during radiation treatment.

NUF2 regulated the progression of hepatocellular carcinoma through modulating the PI3K/AKT pathway via stabilizing ERBB3.

Hepatocellular carcinoma (HCC) is among the most prevalent and lethal cancers worldwide. The NDC80 kinetochore complex component NUF2 has been previously identified as up-regulating in HCC and associated with patient prognosis. However, the pathophysiological effects and molecular mechanisms of NUF2 in tumorigenesis remain unclear. In this study, we confirmed a significant increase in NUF2 expression in HCC tissues and established a correlation between high NUF2 expression and adverse outcomes in HCC patients. Through in vitro and in vivo experiments, we demonstrated that genetic inhibition of NUF2 suppressed the proliferation of HCC cells and disrupted the cell cycle. Further investigation into the molecular mechanisms revealed that NUF2 interacted with ERBB3, inhibiting its ubiquitination degradation, thus activating the PI3K/AKT signaling pathway and influencing cell cycle regulation. Overall, this study revealed the crucial role of NUF2 in promoting the malignant progression of HCC, suggesting its potential as both a prognostic biomarker and a therapeutic target for HCC.

Gut Microbiota Metabolite TMA May Mediate the Effects of TMAO on Glucose and Lipid Metabolism in C57BL/6J Mice.

SCOPE: Gut microbiota can convert a variety of alkaloids and TMAO into TMA, which is then transported by the blood to the liver, and converted into TMAO. In recent years, TMAO has attracted wide attention as a metabolic risk factor in cardiovascular disease, diabetes, and other diseases. However, it is still unclear about the role of gut microbial metabolite TMA in the adverse health impacts of TMAO. METHODS AND RESULTS: Male C57BL/6J is treated with intraperitoneal (i.p.) or oral TMAO for 8 weeks, the area under the OGTT curve of oral group is significantly increased by about 15% compared to the control and injection groups. Serum triglyceride levels in the oral group are significantly higher by 28.2% and 24.6% than those in the control and injection groups, respectively. Meanwhile, cholesterol content in serum is significantly elevated by 27.6% and 30.7%. Similarly, proinflammatory factors gene expressions are significantly increased with oral but not i.p. TMAO intervention. Furthermore, transformation in HepG2 cells shows that TMAO could not be converted into TMA by hepatocytes. CONCLUSION: The adverse effects of TMAO on glucose and lipid metabolism in C57BL/6J mice may act through gut microbiota metabolite TMA.

The Value of the Nutritional Indicators in Predicting Free Flap Failure From a Multicentre Database.

OBJECTIVE: Nutritional and inflammatory statuses have been associated with complications in microvascular-free flaps during head and neck surgeries. This study aimed to evaluate the potential of nutritional indicators in predicting postoperative free flap complications. STUDY DESIGN: We conducted a 20-year retrospective, case-control study within a defined cohort. SETTING: The study involved head and neck cancer patients from the Chang Gung Research Database who underwent simultaneous tumor ablation and free flap wound reconstruction between January 1, 2001, and December 31, 2019. METHODS: We employed logistic regression and stratified analysis to assess the risk of free flap complications and the subsequent need for flap revision or redo in relation to nutritional indicators and other clinical variables. RESULTS: Of the 8066 patients analyzed, 687 (8.5%) experienced free flap complications. Among these, 197 (2.4%) had free flap failures necessitating a redo of either a free flap or a pedicled flap. Beyond comorbidities such as chronic obstructive pulmonary disease, end-stage renal disease, and a history of prior radiotherapy, every 10-unit decrease in the preoperative prognostic nutritional index (PNI) was consistently associated with an increased risk of both free flap complications and failure. The covariate-adjusted odds ratios were 1.90 (95% confidence interval [CI]: 1.42-2.54) and 1.89 (95% CI: 1.13-3.17), respectively. CONCLUSION: A lower preoperative PNI suggests a higher likelihood of microvascular free flap complications in head and neck surgeries. Further randomized controlled trial designs are required to establish causality.

Hedan tablet ameliorated non-alcoholic steatohepatitis by moderating NF-κB and lipid metabolism-related pathways via regulating hepatic metabolites.

Non-alcoholic steatohepatitis (NASH) is a severe form of fatty liver disease. If not treated, it can lead to liver damage, cirrhosis and even liver cancer. However, advances in treatment have remained relatively slow, and there is thus an urgent need to develop appropriate treatments. Hedan tablet (HDP) is used to treat metabolic syndrome. However, scientific understanding of the therapeutic effect of HDP on NASH remains limited. We used HDP to treat a methionine/choline-deficient diet-induced model of NASH in rats to elucidate the therapeutic effects of HDP on liver injury. In addition, we used untargeted metabolomics to investigate the effects of HDP on metabolites in liver of NASH rats, and further validated its effects on inflammation and lipid metabolism following screening for potential target pathways. HDP had considerable therapeutic, anti-oxidant, and anti-inflammatory effects on NASH. HDP could also alter the hepatic metabolites changed by NASH. Moreover, HDP considerable moderated NF-κB and lipid metabolism-related pathways. The present study found that HDP had remarkable therapeutic effects in NASH rats. The therapeutic efficacy of HDP in NASH mainly associated with regulation of NF-κB and lipid metabolism-related pathways via arachidonic acid metabolism, glycine-serine-threonine metabolism, as well as steroid hormone biosynthesis.

Microbiota-derived indoles alleviate intestinal inflammation and modulate microbiome by microbial cross-feeding.

BACKGROUND: The host-microbiota interaction plays a crucial role in maintaining homeostasis and disease susceptibility, and microbial tryptophan metabolites are potent modulators of host physiology. However, whether and how these metabolites mediate host-microbiota interactions, particularly in terms of inter-microbial communication, remains unclear. RESULTS: Here, we have demonstrated that indole-3-lactic acid (ILA) is a key molecule produced by Lactobacillus in protecting against intestinal inflammation and correcting microbial dysbiosis. Specifically, Lactobacillus metabolizes tryptophan into ILA, thereby augmenting the expression of key bacterial enzymes implicated in tryptophan metabolism, leading to the synthesis of other indole derivatives including indole-3-propionic acid (IPA) and indole-3-acetic acid (IAA). Notably, ILA, IPA, and IAA possess the ability to mitigate intestinal inflammation and modulate the gut microbiota in both DSS-induced and IL-10-/- spontaneous colitis models. ILA increases the abundance of tryptophan-metabolizing bacteria (e.g., Clostridium), as well as the mRNA expression of acyl-CoA dehydrogenase and indolelactate dehydrogenase in vivo and in vitro, resulting in an augmented production of IPA and IAA. Furthermore, a mutant strain of Lactobacillus fails to protect against inflammation and producing other derivatives. ILA-mediated microbial cross-feeding was microbiota-dependent and specifically enhanced indole derivatives production under conditions of dysbiosis induced by Citrobacter rodentium or DSS, but not of microbiota disruption with antibiotics. CONCLUSION: Taken together, we highlight mechanisms by which microbiome-host crosstalk cooperatively control intestinal homoeostasis through microbiota-derived indoles mediating the inter-microbial communication. These findings may contribute to the development of microbiota-derived metabolites or targeted "postbiotic" as potential interventions for the treatment or prevention of dysbiosis-driven diseases. Video Abstract.

3D Printing of Flexible BaTiO3/Polydimethylsiloxane Piezocomposite with Aligned Particles for Enhanced Energy Harvesting.

With the rapid development of human-machine interactions and artificial intelligence, the demand for wearable electronic devices is increasing uncontrollably all over the world; however, an unsustainable power supply for such sensors continues to restrict their applications. In the present work, piezoelectric barium titanate (BaTiO3) ceramic powder with excellent properties was prepared from milled precursors through a solid-state reaction. To fabricate a flexible device, the as-prepared BaTiO3 powder was mixed with polydimethylsiloxane (PDMS) polymer. The BaTiO3/PDMS ink with excellent rheological properties was extruded smoothly by direct ink writing technology (DIW). BaTiO3 particles were aligned due to the shear stress effect during the printing process. Subsequently, the as-printed composite was assembled into a sandwich-type device for effective energy harvesting. It was observed that the maximum output voltage and current of this device reached 68 V and 720 nA, respectively, for a BaTiO3 content of 6 vol %. Therefore, the material extrusion-based three-dimensional (3D) printing technique can be used to prepare flexible piezoelectric composites for efficient energy harvesting.

PIN1 promotes the metastasis of cholangiocarcinoma cells by RACK1-mediated phosphorylation of ANXA2.

BACKGROUND: Cholangiocarcinoma (CCA), a primary hepatobiliary malignancy, is characterized by a poor prognosis and a lack of effective treatments. Therefore, the need to explore novel therapeutic approaches is urgent. While the role of Peptidylprolyl Cis/Trans Isomerase, NIMA-Interacting 1 (PIN1) has been extensively studied in various tumor types, its involvement in CCA remains poorly understood. METHODS: In this study, we employed tissue microarray (TMA), reverse transcription-polymerase chain reaction (RT-PCR), and The Cancer Genome Atlas (TCGA) database to assess the expression of PIN1. Through in vitro and in vivo functional experiments, we investigated the impact of PIN1 on the adhesion and metastasis of CCA. Additionally, we explored downstream molecular pathways using RNA-seq, western blotting, co-immunoprecipitation, immunofluorescence, and mass spectrometry techniques. RESULTS: Our findings revealed a negative correlation between PIN1 overexpression and prognosis in CCA tissues. Furthermore, high PIN1 expression promoted CCA cell proliferation and migration. Mechanistically, PIN1 functioned as an oncogene by regulating ANXA2 phosphorylation, thereby promoting CCA adhesion. Notably, the interaction between PIN1 and ANXA2 was facilitated by RACK1. Importantly, pharmacological inhibition of PIN1 using the FDA-approved drug all-trans retinoic acid (ATRA) effectively suppressed the metastatic potential of CCA cells in a nude mouse lung metastasis model. CONCLUSION: Overall, our study emphasizes the critical role of the PIN1/RACK1/ANXA2 complex in CCA growth and functionality, highlighting the potential of targeting PIN1 as a promising therapeutic strategy for CCA.

Programmable Potentials Choreograph Defects in a Colloidal Crystal Shell.

Crystallization on spherical surfaces is obliged by topology to induce lattice defects. But controlling the organization of such defects remains a great challenge due to the long-range constraints of the curved geometry. Here, we report on DNA-coated colloids whose programmable interaction potentials can be used to regulate the arrangement of defects and even achieve perfect icosahedral order on a sphere. Combined simulations and theoretical analysis show how the potential can be tuned by changing the temperature, thereby controlling the number of defects. An explicit expression for the effective potential is derived, allowing us to distinguish the effects of entropic repulsion and enthalpic attraction. Altogether, the present findings provide insights into the physics of crystallization on curved spaces and may be used for designing desired crystal geometries.