Low-grade wind-driven directional flow in anchored droplets.

Low-grade wind with airspeed Vwind < 5 m/s, while distributed far more abundantly, is still challenging to extract because current turbine-based technologies require particular geography (e.g., wide-open land or off-shore regions) with year-round Vwind > 5 m/s to effectively rotate the blades. Here, we report that low-speed airflow can sensitively enable directional flow within nanowire-anchored ionic liquid (IL) drops. Specifically, wind-induced air/liquid friction continuously raises directional leeward fluid transport in the upper portion, whereas three-phase contact line (TCL) pinning blocks further movement of IL. To remove excessive accumulation of IL near TCL, fluid dives, and headwind flow forms in the lower portion, as confirmed by microscope observation. Such stratified circulating flow within single drop can generate voltage output up to ~0.84 V, which we further scale up to ~60 V using drop "wind farms". Our results demonstrate a technology to tap the widespread low-grade wind as a reliable energy resource.

The attenuated hepatic clearance of propionate increases cardiac oxidative stress in propionic acidemia.

Propionic acidemia (PA), arising from PCCA or PCCB variants, manifests as life-threatening cardiomyopathy and arrhythmias, with unclear pathophysiology. In this work, propionyl-CoA metabolism in rodent hearts and human pluripotent stem cell-derived cardiomyocytes was investigated with stable isotope tracing analysis. Surprisingly, gut microbiome-derived propionate rather than the propiogenic amino acids (valine, isoleucine, threonine, and methionine) or odd-chain fatty acids was found to be the primary cardiac propionyl-CoA source. In a Pcca-/-(A138T) mouse model and PA patients, accumulated propionyl-CoA and diminished acyl-CoA synthetase short-chain family member 3 impede hepatic propionate disposal, elevating circulating propionate. Prolonged propionate exposure induced significant oxidative stress in PCCA knockdown HL-1 cells and the hearts of Pcca-/-(A138T) mice. Additionally, Pcca-/-(A138T) mice exhibited mild diastolic dysfunction after the propionate challenge. These findings suggest that elevated circulating propionate may cause oxidative damage and functional impairment in the hearts of patients with PA.

Constructing green superhydrophilic and superoleophobic COFs-MOFs hybrid-based membrane for efficiently emulsion separation and synchronous removal of microplastics, dyes, and pesticides.

Oil spills and micropollutants have become thorny environmental issues, posing serious threat to ecosystem and human health. To settle such dilemma, this study successfully constructed a robust and environmentally-friendly MOFs-COFs hybrid-based membrane (FS-50/COF(MATPA)-MOF(Zr)/PDA@PVDF) for the first time through solution synthesis and solvothermal method, combined with surface modification of FS-50 molecule. Importantly, we employed a simple two-step strategy to obtain the high-aspect-ratio MOFs fibers: (1) solvent regulation to generate smaller needle-like whiskers during the in-situ growth of MOFs on COFs; (2) high pressure induced directional crystallization in filtration process. The introduction of polydopamine (PDA) greatly improved the adhesion between coating and PVDF membrane. The in-situ growth of high length-diameter ratio MOFs fibers on blocky COFs greatly enhanced the specific surface area of MOFs-COFs hybrid, thus provided sufficient absorption sites. The functional groups of FS-50 endowed the hybrid membrane with superhydrophilicity and superoleophobicity, which facilitated to selectively penetrate water molecules and repel non-polar pollutants. The separation efficiency and decontamination mechanism of hybrid membrane to the simulated oily wastewater (containing various MPs, dyes, and pesticides) were investigated through experiments and theoretical calculations. The hybrid membrane could selectively and synchronously adsorb various dyes (20 mg/L-120 mg/L, almost 100% removal) and pesticides (10 mg/L for DIF and TET, adsorption rates 93.2% and 90.9%, respectively) from oil-water emulsion (50 mL). The large-scale coated sponge (6 cm × 4.5 cm × 3 cm) could quickly achieve separation of oil-water mixture (almost 100%) with a water permeability of more than 162 L m-2·h-1·bar-1, and simultaneously remove various MPs (PP-2000, PP-100, PE-2000, PS-100, 0.2 g/300 mL for each), Sudan Ⅲ (C0 = 200 mg/L), and DIF (C0 = 10 mg/L) from a simulant oily wastewater (300 mL), with the removal rates of almost 100% for MPs, 99.7% for Sudan Ⅲ, and 95.8% for DIF. Furthermore, we elucidated the removal mechanism of pesticide and dyes through simulating the theoretical adsorption energy and potential adsorption sites. The hybrid membrane not only provides a promising candidate for the removal of multiple pollutants from oil-water emulsion, but also opens a new strategy for achieving efficient and clean aquatic environment restoration.

Discovery of novel bicyclic[3.3.0]proline peptidyl α-ketoamides as potent 3CL-protease inhibitors for SARS-CoV-2.

The outbreak of SARS-CoV-2 has caused global crisis on health and economics. The multiple drug-drug interaction risk associated with ritonavir warrants specialized assessment before using Paxlovid. Here we report a multiple-round SAR study to provide a novel bicyclic[3.3.0]proline peptidyl α-ketoamide compound 4a, which is endowed with excellent antiviral activities and pharmacokinetic properties. Also, in vivo HCoV-OC43 neonatal mice model demonstrated compound 4a has good in vivo efficacy. Based on these properties, compound 4a worth further SAR optimization with the goal to develop compounds with better pharmacokinetic properties and finally to realize single agent efficacy in human.

Transitional basal cells at the squamous-columnar junction generate Barrett's oesophagus.

In several organ systems, the transitional zone between different types of epithelium is a hotspot for pre-neoplastic metaplasia and malignancy, but the cells of origin for these metaplastic epithelia and subsequent malignancies remain unknown. In the case of Barrett's oesophagus, intestinal metaplasia occurs at the gastro-oesophageal junction, where stratified squamous epithelium transitions into simple columnar cells. On the basis of a number of experimental models, several alternative cell types have been proposed as the source of this metaplasia but in all cases the evidence is inconclusive: no model completely mimics Barrett's oesophagus in terms of the presence of intestinal goblet cells. Here we describe a transitional columnar epithelium with distinct basal progenitor cells (p63+KRT5+KRT7+) at the squamous-columnar junction of the upper gastrointestinal tract in a mouse model. We use multiple models and lineage tracing strategies to show that this squamous-columnar junction basal cell population serves as a source of progenitors for the transitional epithelium. On ectopic expression of CDX2, these transitional basal progenitors differentiate into intestinal-like epithelium (including goblet cells) and thereby reproduce Barrett's metaplasia. A similar transitional columnar epithelium is present at the transitional zones of other mouse tissues (including the anorectal junction) as well as in the gastro-oesophageal junction in the human gut. Acid reflux-induced oesophagitis and the multilayered epithelium (believed to be a precursor of Barrett's oesophagus) are both characterized by the expansion of the transitional basal progenitor cells. Our findings reveal a previously unidentified transitional zone in the epithelium of the upper gastrointestinal tract and provide evidence that the p63+KRT5+KRT7+ basal cells in this zone are the cells of origin for multi-layered epithelium and Barrett's oesophagus.

Relationship between illness perception and family resilience in gynecologic cancer patients: the mediating role of couple illness communication.

OBJECTIVE: To analyze the current family resilience levels of Chinese patients with gynecologic cancer and explore the mediating role of couple illness communication between illness perception and family resilience to facilitate patient adaptation to cancer. METHODS: A total of 310 patients with gynecologic cancer were selected from the gynecology ward of a tertiary care hospital in Jinan, Shandong Province, China. All participants provided their demographic and clinical information and completed the Brief Illness Perception Questionnaire (BIPQ), Couples' Illness Communication Scale (CICS), and Family Hardiness Index (FHI). The mediating effect of couple illness communication was analyzed using SPSS26.0 and Amos21.0. RESULTS: The family resilience score of patients with gynecologic cancer was moderate (55.78 ± 8.65). Illness perception was negatively correlated with couple illness communication(p < 0.05) and family resilience(p < 0.01), while couple illness communication was positively correlated with family resilience (p < 0.01). Couple illness communication mediated the relationship between illness perception and family resilience [ß = - 0.071; 95% confidence interval: (- 0.127)-(- 0.013)]. CONCLUSIONS: The family resilience of patients with gynecologic cancer must be further improved. Since couple illness communication mediates the relationship between illness perception and family resilience in this population, it is important to improve patients' illness perceptions and couple illness communication to enhance their family resilience.

Couple communication quality and family resilience among Chinese gynecologic cancer patients and their spouses: a dyadic study.

PURPOSE: The purpose of this study was to explore the couple communication process for gynecologic cancer (GC) patients and their spouses. Particular attention was given to examining the relationship between couple communication quality and family resilience for GC dyads. METHODS: In this cross-sectional study, 354 dyads were recruited from a gynecology ward of a public hospital in China. The patients and their spouses completed the Couples' Communication Quality Scale and the Family Hardiness Index. This study used the actor-partner interdependence model (APIM) to examine the effect of couple communication quality on family resilience in distinguishable GC dyads. RESULTS: Both GC patients and their spouses reported a moderate level of couple communication quality and family resilience, but spouses reported better couple communication and family resilience than patients. With the exception of perceived response, for which only a patient actor effect was observed, the factors of couple communication quality had significant actor effects on family resilience for both patients and spouses. Additionally, four significant partner effects were found: spouse self-disclosure, stress coping, and productive action positively predicted patients' family resilience, while patient normalcy crafting positively predicted spouses' family resilience. CONCLUSION: This study not only highlights the need for couple-based communication strategies for developing family resilience but also identifies differences in the experiences of patients and their partners, which provides a direction for future intervention research. Through the development of interventions at a dyadic level, spouses can be encouraged to actively engage in communication, which may promote mutual family resilience in a larger sense.

Lymphatic Drainage System and Lymphatic Metastasis of Cancer Cells in the Mouse Esophagus.

BACKGROUND: Lymphatic metastasis is commonly seen in patients with esophageal squamous cell carcinoma (ESCC). Both lymphatic metastasis and the number of involved nodes are prognostic for post-operative survival. To better understand lymphatic metastasis of ESCC, there is a need to develop proper animal models. AIMS: This study is aimed to characterize the morphology and function of the lymphatic drainage system in the mouse esophagus. METHODS: Immunostaining and fluorescence imaging were used to visualize the lymphatic drainage system in the mouse esophagus. Tracers and cancer cells were orthotopically inoculated into the submucosa of the mouse esophagus to mimic lymphatic metastasis of T1 ESCC. RESULTS: Using immunostaining of a lymphatic vessel marker (LYVE1), we found that lymphatic vessels were located in the submucosa and muscularis propria of the mouse esophagus, similar to the human esophagus. In the esophagus of ProxTom mice expressing tdTomato in the lymphatic vessels, we discovered a microscopic meshwork of lymphatic vessels. Functionally, orthotopically inoculated tracers (Indian ink and FITC-dextran) were drained from the submucosa into peri-esophageal lymph nodes via lymphatic vessels. Orthotopically inoculated mouse cancer cells (LLC-eGFP, MOC2) metastasized from the submucosa to lymphatic vessels, peri-esophageal lymph nodes, and distant organs (liver and lung) in immunocompetent mice. Similarly, in immunodeficient mice, orthotopically inoculated human ESCC cells (KYSE450-eGFP-Luc) metastasized via the same route. CONCLUSION: We have characterized the morphology and function of the lymphatic drainage system of the mouse esophagus. These observations lay a foundation for mechanistic and therapeutic studies on lymphatic metastasis of T1 ESCC.

Inhibition of gingival fibroblast necroptosis mediated by RIPK3/MLKL attenuates periodontitis.

AIM: Necroptosis participates in the pathogenesis of many inflammatory diseases, including periodontitis. Here, we aimed to investigate the role and mechanism of necroptosis inhibitors in attenuating periodontitis. MATERIALS AND METHODS: The Gene Expression Omnibus (GEO) dataset GSE164241 was re-analysed to identify the role of necroptosis in periodontitis. Gingival specimens from healthy subjects or periodontitis patients were collected to evaluate the expression level of necroptosis-associated proteins. The therapeutic effect of necroptosis inhibitors on periodontitis was assessed in vivo and in vitro. Moreover, Transwell assays and Western blotting and siRNA transfection were used to identify the effects of necroptotic human gingival fibroblasts (hGFs) on THP-1 macrophages. RESULTS: Re-analysis revealed that gingival fibroblasts (GFs) in periodontitis gingiva showed the highest area under the curve score of necroptosis. Elevated levels of necroptosis-associated proteins were identified in GFs in periodontitis gingiva collected from patients and mice. In ligature-induced periodontitis mice, local administration of receptor interacting protein kinase 3(RIPK3) inhibitor GSK'872 or sh-mixed-lineage kinase domain-like pseudokinase (Mlkl) markedly abrogated necroptosis and rescued periodontitis. Analogously, necroptosis inhibitors alleviated the inflammatory response and release of damage-associated molecular patterns in lipopolysaccharide- or LAZ (LPS + AZD'5582 + z-VAD-fmk, necroptosis inducer)-induced GFs and then reduced THP-1 cell migration and M1 polarization. CONCLUSIONS: Necroptosis in GFs aggravated gingival inflammation and alveolar bone loss. Necroptosis inhibitors attenuate this process by modulating THP-1 macrophage migration and polarization. This study offers novel insights into the pathogenesis and potential therapeutic targets of periodontitis.

Blood urea nitrogen to creatinine ratio is associated with physical frailty in older-aged Chinese: a cross-sectional study.

BACKGROUND: The relationship between the ratio of blood urea nitrogen to creatinine (BUN/Cr) and physical frailty in elderly patients remains unclear. The study aims to investigate the association between the BUN/Cr ratio and physical frailty in the elderly Chinese population. METHODS: In this cross-sectional analysis, the clinical data of 5213 participants from 2015 were selected from the China Health and Retirement Longitudinal Study (CHARLS). The demographic variables (including age and gender) and health behavior (including smoking and drinking history), anthropometric (including systolic and diastolic blood pressure, waist circumference (WC), etc.), physical performances (i.e., grip strength, repeated chair stands, etc.), and biochemical indicators (i.e., blood urea nitrogen (BUN), creatinine(Cr), total cholesterol (TC), triglycerides (TG), etc.) were measured. The association between the BUN/Cr ratio and physical frailty was analyzed. RESULTS: After adjusting for potential confounding factors, smooth curve fitting showed a linear relationship between the BUN/Cr ratio and grip strength, a non-linear relationship between the BUN/Cr ratio, and repeated chair-rising time. The fully adjusted linear regression results showed a negative association between the BUN/Cr ratio and grip strength. In the multivariate, piecewise linear regression, when the BUN/Cr ratio was greater than 18.60, the repeated chair-rising time increased with the increase in BUN/Cr ratio (ß = 0.046, 95%CI 0.025, 0.066; p < 0.001). However, we did not observe a significant correlation when the BUN/Cr ratio was less than 18.60 (ß = -0.007, 95%CI -0.046, 0.032; p = 0.717). CONCLUSION: This study demonstrated that the BUN/Cr ratio might be associated with physical frailty in older-aged Chinese, and this association requires further investigation.

Surgical outcomes of percutaneous endoscopic thoracic decompression in the treatment of multi-segment thoracic ossification of the ligamentum flavum.

BACKGROUND: Previous studies have demonstrated satisfactory outcomes of percutaneous endoscopic thoracic decompression (PETD) for single-segment thoracic ossification of the ligamentum flavum (TOLF). However, the clinical outcomes of PETD in patients with multi-segment TOLF (mTOLF) remain unclear. The aim of the present study was to evaluate the efficacy and safety of PETD for patients with multi-segment mTOLF. METHODS: Eighteen consecutive patients (41 segments) with mTOLF were treated with PETD between January 2020 and December 2021. The clinical outcomes were evaluated using the modified Japanese Orthopaedic Association (mJOA) score and Visual Analog Scale (VAS), whereas radiographic parameters were measured by cross-section area of the spinal canal and anteroposterior diameter of the spinal cord. RESULTS: The follow-up period ranged from 14 to 34 months. The mean operation time and blood loss were 154.06 ± 32.14 min and 61.72 ± 12.72 ml, respectively. Hospital stay after first-stage operation was 10.89 ± 2.42 days. The mJOA score and VAS score significantly improved at the final follow-up, with a mean mJOA recovery rate of 63.3 ± 21.90%. The incidence of complications was 12.2% per level. The radiographic outcomes showed adequate decompression of the spinal cord. CONCLUSIONS: The present study demonstrates that PETD is effective and safe as a minimally invasive procedure to treat patients with mTOLF. All patients showed relief of their symptoms and improvement in neurological function.

Seed-Assisted Synthesis of Hierarchically Structured Nano-Sized Ti-ß Zeolites for the Efficient Epoxidation Reaction of Alkenes.

The development of nano-sized titanosilicate zeolites with hierarchical structures is crucial in promoting the efficient epoxidation of alkenes. In the present work, nano-sized hierarchical Ti-ß (*BEA) zeolites with high crystal yield are prepared by a one-pot nanoseed-assisted approach. The influence of seed size on the resultant Ti-ß zeolites is investigated by complementary characterizations, including X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), N2 adsorption/desorption, UV-vis diffuse reflectance spectroscopy (DRS), and UV Raman spectroscopy. The possible process for the formation of hierarchical Ti-ß nanocrystals with the assistance of nanoseeds in the synthesis gel is proposed. Consequentially, the nano-sized hierarchical material prepared by the nanoseed-assisted method shows excellent mass transportation and accessibility to active sites by reducing particle size and constructing hierarchical porosity, hence showing a remarkably enhanced catalytic activity and selectivity in the epoxidation reaction of alkenes. This work will shed light on the efficient preparation of nano-sized titanosilicate zeolites.

Alcohol drinking inhibits NOTCH-PAX9 signaling in esophageal squamous epithelial cells.

Alcohol drinking has been established as a major risk factor for esophageal diseases. Our previous study showed that ethanol exposure inhibited PAX9 expression in human esophageal squamous epithelial cells in vitro and in vivo. In this study, we aimed to investigate the molecular pathways through which alcohol drinking suppresses PAX9 in esophageal squamous epithelial cells. We first demonstrated the inhibition of NOTCH by ethanol exposure in vitro. NOTCH regulated PAX9 expression in KYSE510 and KYSE410 cells in vitro and in vivo. RBPJ and NOTCH intracellular domain (NIC) D1 ChIP-PCR confirmed Pax9 as a direct downstream target of NOTCH signaling in mouse esophagus. NOTCH inhibition by alcohol drinking was further validated in mouse esophagus and human tissue samples. In conclusion, ethanol exposure inhibited NOTCH signaling and thus suppressed PAX9 expression in esophageal squamous epithelial cells in vitro and in vivo. Our data support a novel mechanism of alcohol-induced esophageal injury through the inhibition of NOTCH-PAX9 signaling. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Dyadic communication quality and family resilience in gynecologic cancer survivors: a study on the mediating role of perceived spousal support.

PURPOSE: To analyze the level of family resilience in Chinese gynecological cancer survivors and determine whether perceived spousal support plays a mediating role in the relationship between dyadic communication quality and family resilience, enhance the confidence of families in coping with the disease together, and thus promote psychosocial adaptation to cancer. METHODS: A total of 348 gynecologic cancer survivors were selected from a gynecologic ward in a public hospital in Shandong Province, China. All participants completed the Sociodemographic and Clinical Characteristics Questionnaire, Couples' Communication Quality Scale (CCQS), Perceived Social Support Scale (PSSS), and Family Hardiness Index (FHI). The mediating effect of perceived spousal support was estimated using the bootstrap method via IBM SPSS AMOS 21.0. RESULTS: The mean FHI score was 53.03 ± 9.34 points, showing moderate levels of family resilience. Family resilience was shown to be significantly positively associated with both perceived spousal support and dyadic communication quality (both p < 0.01). Furthermore, perceived spousal support was shown to partially mediate the relationship between communication quality and family resilience (ß = 0.141; 95% confidence interval: 0.063-0.243). CONCLUSION: The level of family resilience in survivors of gynecologic cancer needs to be further improved, and perceived spousal support partially mediates the relationship between dyadic communication quality and family resilience within this population. Therefore, dyadic communication quality and subjective perceived spousal support should be enhanced for gynecologic cancer survivors to increase their family resilience.

Transcranial random noise stimulation and exercise do not modulate ocular dominance plasticity in adults with normal vision.

Short-term deprivation of one eye by monocular patching causes a temporary increase in the contribution of that eye to binocular vision when the eye patch is removed. This effect, known as ocular dominance plasticity, provides a model of neuroplasticity within the human binocular visual system. We investigated whether physical exercise and the non-invasive brain stimulation technique transcranial random noise stimulation (tRNS), two interventions that may increase visual cortex neuroplasticity, enhance ocular dominance plasticity when delivered individually or in combination. Ocular dominance was measured using a grating rivalry test and a dichoptic letter contrast polarity judgment test. We observed robust ocular dominance changes for both outcome measures following 2-hour monocular deprivation; however, the magnitude of the effect was not influenced by exercise or tRNS. Ocular dominance plasticity may already be maximal after 2 hours of monocular deprivation in those with normal vision and therefore cannot be augmented by interventions designed to enhance neuroplasticity.

One-Step Carbonization Synthesis of Magnetic Biochar with 3D Network Structure and Its Application in Organic Pollutant Control.

In this study, a magnetic biochar with a unique 3D network structure was synthesized by using a simple and controllable method. In brief, the microbial filamentous fungus Trichoderma reesei was used as a template, and Fe3+ was added to the culture process, which resulted in uniform recombination through the bio-assembly property of fungal hyphae. Finally, magnetic biochar (BMFH/Fe3O4) was synthesized by controlling different heating conditions in a high temperature process. The adsorption and Fenton-like catalytic performance of BMFH/Fe3O4 were investigated by using the synthetic dye malachite green (MG) and the antibiotic tetracycline hydrochloride (TH) as organic pollutant models. The results showed that the adsorption capacity of BMFH/Fe3O4 for MG and TH was 158.2 and 171.26 mg/g, respectively, which was higher than that of most biochar adsorbents, and the Fenton-like catalytic degradation effect of organic pollutants was also better than that of most catalysts. This study provides a magnetic biochar with excellent performance, but more importantly, the method used can be effective in further improving the performance of biochar for better control of organic pollutants.

Cow Dung-Based Biochar Materials Prepared via Mixed Base and Its Application in the Removal of Organic Pollutants.

Cow dung (CD) is a waste product of livestock production. Improper disposal of a large amount of CD will cause environmental pollution. In this work, three biochar materials based on CD (BMCD) were prepared by using three types of base, including KOH, NaOH, and mixed base (MB, a mixture of equal mass NaOH and KOH) as activators to investigate the different physicochemical properties of BMCDs (BMCD-K, BMCD-Na, and BMCD-MB). The objective was to verify the effectiveness of MB activation in the preparation of biochar materials. The results show that MB has an effect on the structural characteristics of BMCDs. In particular, the surface area and total pore volume, the specific surface area, and the total pore volume of BMCD-MB (4081.1 m2 g-1 and 3.0118 cm3 g-1) are significantly larger than those of BMCD-K (1784.6 m2 g-1 and 1.1142 cm3 g-1) and BMCD-Na (1446.1 m2 g-1 and 1.0788 cm3 g-1). While synthetic dye rhodamine B (RhB) and antibiotic tetracycline hydrochloride (TH) were selected as organic pollutant models to explore the adsorption performances, the maximum adsorption capacities of BMCD-K, BMCD-NA and BMCD-MB were 951, 770, and 1241 mg g-1 for RhB, 975, 1051, and 1105 mg g-1 for TH, respectively, which were higher than those of most adsorbents. This study demonstrated that MB can be used as an effective activator for the preparation of biochar materials with enhanced performance.

PAX9 in Cancer Development.

Paired box 9 (PAX9) is a transcription factor of the PAX family functioning as both a transcriptional activator and repressor. Its functional roles in the embryonic development of various tissues and organs have been well studied. However, its roles and molecular mechanisms in cancer development are largely unknown. Here, we review the current understanding of PAX9 expression, upstream regulation of PAX9, and PAX9 downstream events in cancer development. Promoter hypermethylation, promoter SNP, microRNA, and inhibition of upstream pathways (e.g., NOTCH) result in PAX9 silencing or downregulation, whereas gene amplification and an epigenetic axis upregulate PAX9 expression. PAX9 may contribute to carcinogenesis through dysregulation of its transcriptional targets and related molecular pathways. In summary, extensive studies on PAX9 in its cellular and tissue contexts are warranted in various cancers, in particular, HNSCC, ESCC, lung cancer, and cervical SCC.

Host versus cell-dependent effects of ß-arrestin 1 expression in prostate tumorigenesis.

Prostate cancer (PCa) constitutes a serious health challenge and remains one of the main causes of cancer-related death among men. The more aggressive form of the disease has been attributed to androgen independence, resulting in a lack of response to androgen deprivation therapy and sustained activation of other growth pathways. The scaffold proteins ß-arrestin 1 and 2 (ßarr1 and ßarr2), which are known to mediate G protein-coupled receptor desensitization and internalization, were also shown to modulate prostate tumorigenesis. ßarr1 is significantly overexpressed (>4-fold) in PCa cells relative to ßarr2. In this study, we investigated the effect of ßarr1 overexpression in PCa development and progression using the mouse and human PCa cell xenografts, and autochthonous transgenic adenocarcinoma of the mouse prostate (TRAMP) models deficient in ß-arrestin depletion of ßarr1 in TRAMP mice (TRAMP/ßarr1-/-) increased PCa growth and decreased overall survival relative to control TRAMP or TRAMP/ßarr2-/- animals. Prostate tissues from TRAMP/ßarr1-/- tumors displayed an increase in androgen receptor (AR) expression, whereas overexpression of ßarr1 in TRAMP-C1 (TRAMP-C1-ßarr1-GFP) which derived from TRAMP decreased AR expression, cell proliferation and tumor growth in nude mice xenografts, relative to control TRAMP-C1-GFP. Knockdown of ßarr1 expression in human MDA PCa 2b cells (MDA PCa 2b-ßarr1-/-) also decreased AR expression cell proliferation and tumor growth relative to control (MDA PCa 2b-Sham) cells. Interestingly, both TRAMP-C1-ßarr1-GFP and MDA PCa 2b-ßarr1-/- xenografts showed a decrease in AKT phosphorylation but an increase in MAPK activation. Altogether, the data indicate that the effect of ßarr1 in modulating AR signaling to regulate PCa aggressiveness is cell and host autonomous.

Research on esophageal cancer: With personal perspectives from studies in China and Kenya.

The most common form of esophageal cancer (EC), esophageal squamous cell carcinoma (ESCC), is prevalent in many unindustrialized societies, among people with lower socioeconomic status and those who frequently use tobacco and alcohol. In some areas, ESCC mortality ranked top among all cancer. In this review, we begin with discussions of the extensive research on EC in Linxian in northern China that started 60 years ago and the recent studies in Kenya from our personal perspectives. Based on the results obtained from these studies and information from the literature, we summarize our current understanding about the risk factors for ESCC including lifestyle factors (smoking, alcohol, consumption of food and beverages at high temperature and other unhealthy habits), poor diet and nutritional insufficiencies and genetic susceptibility. Elimination or minimization of these environmental risk factors, as well as early detection and treatment of precancerous lesions, would be effective means for the prevention of ESCC. Current knowledge of molecular alterations in ESCC (gene mutations, hypermethylation and amplification or overexpression), as well as treatment of ESCC and the potential of targeted therapy, are also discussed. Finally, we propose effective approaches for the prevention of ESCC by adapting a healthy lifestyle, including a healthy diet that would also prevent other diseases. Community outreach, public education and international collaboration are important for achieving this public health goal.