Theoretical Investigation on the Reversible Photoswitch Mechanism of Benzylidene-Oxazolone System.

The design and application of molecular photoswitches have attracted much attention. Herein, we performed a detailed computational study on the photoswitch benzylidene-oxazolone system based on static electronic structure calculations and on-the-fly excited-state dynamic simulations. For the Z and E isomer, we located six and four minimum energy conical intersections (MECIs) between the first excited state (S1) and the ground state (S0), respectively. Among them, the relaxation pathway driven by ring-puckering motion is the most competitive channel with the photoisomeization process, leading to the low photoisomerization quantum yield. In the dynamic simulations, about 88 % and 66 % trajectories decays from S1 to S0 for Z and E isomer, respectively within the total simulation time of ~2 ps. The photoisomeization quantum yields obtained in our study (0.20 for Z→E and 0.12 for E→Z) agree well with the experimental measured values (0.25 and 0.11), even though the number of trajectories are limited to 50. Our study sheds light on the complexity of the benzylidene-oxazolone system 's deactivation process and the competitive mechanisms among different reaction channels, which provide theoretical guidance for further design and development of benzylidene-oxazolone based molecular photoswitches.

Methods to assess tooth gingival thickness and diagnose gingival phenotypes: A systematic review.

OBJECTIVE: Measurement of the periodontal soft tissue dimension is crucial for clinical decision-making and aesthetic prognosis. However, the effectiveness of different measuring methods remains unclear. This systematic review aimed to explore the diagnostic accuracy of two non-invasive methods (namely CBCT and ultrasound) for gingival thickness measurement at different tooth positions. MATERIALS AND METHODS: A systematic search was performed using PubMed (including Medline), PubMed Central, OVID, Cochrane Library, LILACS and OpenGrey. Studies focusing on comparisons between CBCT, ultrasound and direct transgingival probing were included. The means, SDs and correlation coefficients with 95% confidence intervals were extracted and analyzed using Review Manager and R software. RESULTS: Twelve studies were selected. No significant difference was found between CBCT measurement and transgingival probing in the anterior and posterior dentition, and a moderate correlation was observed between these two methods (r = 0.41). A weak correlation was found between ultrasound measurement and transgingival probing (r = 0.32), and a slight but statistically significant difference was found when comparing ultrasonic devices and transgingival probing in the posterior area. CONCLUSION: CBCT can be considered a relatively reliable method for gingival thickness measurement in both the anterior and posterior areas compared with direct probing. Ultrasonic devices provide limited accuracy in the posterior area but are relatively comparable with direct clinical assessments in the anterior area. CLINICAL SIGNIFICANCE: Measurement location may affect the diagnostic accuracy and repeatability of gingival thickness measurements. Appropriate method selection in different clinical scenarios is crucial to aesthetic outcome prediction and decision-making.

Enhanced Circadian Clock in MSCs-Based Cytotherapy Ameliorates Age-Related Temporomandibular Joint Condyle Degeneration.

Aging has been proven to be one of the major causes of temporomandibular joint (TMJ) disability and pain in older people. Peripheral circadian rhythms play a crucial role in endochondral ossification and chondrogenesis. However, the age-related alterations of circadian clock in TMJ structures are seldom reported. In the current study, TMJ condyles were extracted from young (4-month-old), middle-aged (10-month-old), and old-aged (20-month-old) adults to detect the morphology and circadian oscillation changes in TMJ condyles with aging. The transcriptome profile of Bmal1-deleted bone-marrow mesenchymal stem cells (BMSCs) and controls were explored to reveal the circadian-related differences at the molecular level. Furthermore, the reparative effects of Bmal1-overexpressed BMSCs-based cytotherapy in aged TMJ condyles were investigated in vitro and in vivo. Aged TMJ condyles displayed damaged tissue structure and an abolished circadian rhythm, accompanied by a progressively decreasing chondrogenesis capability and bone turnover activities. The deletion of Bmal1 significantly down-regulated chondrogenesis-related genes Prg4, Sox9, and Col7a1. Bmal1-overexpressed BMSCs presented improved migration capability ex vivo and attenuated age-related TMJ condylar degeneration in vivo. These data demonstrate the crucial role of circadian timing in the maintenance of osteochondral homeostasis, and indicate the potential clinical prospects of circadian-modified MSCs therapy in tissue regeneration.

Comparison of Multiple Quantitative Evaluation Indices of Theoretical Knowledge and Clinical Practice Skills and Training of Medical Interns in Cardiovascular Imaging Using Blended Teaching and the Case Resource Network Platform (CRNP).

BACKGROUND This study aimed to compare multiple quantitative evaluation indices of levels of theoretical knowledge and clinical practice skills in training medical interns in cardiovascular imaging based on the use of the blended teaching (BT) online artificial intelligence (AI) case resource network platform (CRNP), including time and frequency indices and effectiveness of the CRNP. MATERIAL AND METHODS The study included 110 medical interns who were divided into the routine teaching (RT) group (n=55) and the blended teaching (BT) group (n=55). The two were assessed using the mini-clinical evaluation exercise (mini-CEX) that assessed clinical skills, attitudes, and behaviors and using an objective written questionnaire. The following four indices were compared between the RT and BT groups: the X-ray score (XS), the computed tomography angiography (CTA) score (CS), the cardiac magnetic resonance imaging (CMRI) score (MS), and the average score (AS). Seven assessment indicators included: the imaging description (ID), the qualitative diagnosis (QD), the differential diagnosis (DD), examination preparation (EP), interview skill (IS), position display (PD), and human care (HC). Indicators of CRNP use included: number of times (TN), average duration (AD), single maximum duration (SMD), and total duration (TD). RESULTS AS significantly correlated with AD (rAD=0.761) and TD (rTD=0.754), and showed moderate correlation with TN (rTN=0.595), but weak correlation with SMD (rSMD=0.404). CONCLUSIONS Levels of theoretical knowledge and clinical practice skills during medical intern training in cardiovascular imaging based on BT using the CRNP teaching technology improved theoretical knowledge and practical skills.

Effect of ultrasound-assisted Maillard reaction on glycosylation of goat whey protein: Structure and functional properties.

Goat whey protein (GWP) has a rich amino acid profile and good techno-functional attributes but still has limited functional performance for certain applications. This study introduces an innovative ultrasound-assisted Maillard reaction to enhance GWP's functional properties by conjugating it with either gum Arabic (GA) or citrus pectin (CP). Sonication accelerated the Maillard reaction, and the glycosylation of GWP was significantly enhanced after optimization of the conjugation conditions. Gel electrophoresis examination verified the creation of GWP-polysaccharide conjugates, while scanning electron microscopy analysis revealed structural modifications caused by polysaccharide grafting and sonication. The use of ultrasound in the Maillard reaction notably enhanced the solubility, foaming capacity, and emulsifying attributes of the GWPs. Among the conjugates, the GWP-GA ones exhibited the best functional properties. Our findings suggest that this approach can notably improve the functional attributes of GWPs, thus broadening their potential uses in the food sector and beyond.

Regulating protein corona on nanovesicles by glycosylated polyhydroxy polymer modification for efficient drug delivery.

The dynamic protein corona formed on nanocarriers has been revealed to strongly affect their in vivo behaviors. Precisely manipulating the formation of protein corona on nanocarriers may provide an alternative impetus for specific drug delivery. Herein, we explore the role of glycosylated polyhydroxy polymer-modified nanovesicles (CP-LVs) with different amino/hydroxyl ratios in protein corona formation and evolution. CP-LVs with an amino/hydroxyl ratio of approximately 0.4 (CP1-LVs) are found to efficiently suppress immunoglobulin adsorption in blood and livers, resulting in prolonged circulation. Moreover, CP1-LVs adsorb abundant tumor distinctive proteins, such as CD44 and osteopontin in tumor interstitial fluids, mediating selective tumor cell internalization. The proteins corona transformation specific to the environment appears to be affected by the electrostatic interaction between CP-LVs and proteins with diverse isoelectric points. Benefiting from surface modification-mediated protein corona regulation, paclitaxel-loaded CP1-LVs demonstrate superior antitumor efficacy to PEGylated liposomes. Our work offers a perspective on rational surface-design of nanocarriers to modulate the protein corona formation for efficient drug delivery.

Silk fibroin-based colorimetric microneedle patch for rapid detection of spoilage in packaged salmon samples.

Spoiled salmon can cause foodborne diseases and severely affects human health. Herein, we report a pH-responsive colorimetric microneedle (MN) patch fabricated from bromothymol blue (BTB) and silk fibroin meth acryloyl (SilMA) (BTB/SilMA@MN patch) for sensing salmon spoilage. The needle tips of MN could penetrate food cling film and insert into fish to extract tissue fluids directly and transport the extracted fluids to the backing layer for color displaying. The color change of BTB/SilMA@MN patches depended on the pH variation resulting from the increase of total volatile basic nitrogen in salmon during storage. The color of MN patches changed from yellow to yellowish green and to final green, indicating salmon changed from fresh to medium fresh and then to putrefied, respectively. Salmon spoilage can be rapidly determined via naked eye recognition and also analyzed on a smartphone in a nondestructive way, allowing consumers to estimate food quality easily and reliably.

Co-delivery of curcumin and epigallocatechin gallate in W/O/W emulsions stabilized by protein fibril-cellulose complexes.

Hydrophobic curcumin and hydrophilic epigallocatechin gallate (EGCG) are reported to exhibit a variety of biological activities and may exhibit synergistic effects when used in combination. A co-encapsulation system was developed to improve their applicability and bioavailability. This delivery system consisted of a water-in-oil-in-water (W1/O/W2) double emulsion stabilized by whey protein isolate fibrils (WPIFs) and cellulose nanocrystals (CNCs). Double emulsions were fabricated using a two-step emulsification method using either WPIF-CNC complexes or WPIF alone. The physicochemical stability, encapsulation performance, and digestive properties of the delivery systems were then investigated. The double emulsions stabilized by the WPIF-CNC complexes were more resistant to heat and salt stress, exhibited greater encapsulation stability, and had a higher bioaccessibility for curcumin (67.8%) and EGCG (68.9%) than those stabilized by WPIFs. This research shows that the stability and bioaccessibility of curcumin and EGCG can be enhanced by co-encapsulating them in emulsion-based delivery systems using nanostructured protein-polysaccharide complexes.

Periodontal bone regeneration with a degradable thermoplastic HA/PLCL bone graft.

Strategic bone grafts are required to regenerate periodontal bone defects owing to limited self-healing. Current bioceramic particle or deproteinized bovine bone (DBB) products are not able to ideally meet clinical requirements, such as insufficient operability and slow degradation rates. Herein, a strong-interacted bone graft was designed and synthesized by modifying hydroxyapatite (HA) with a lactide-caprolactone copolymer (PLCL) to improve component homogeneity and mechanical properties. The physical-chemical analysis indicated that HA particles were homogenously distributed in HA/PLCL bone grafts, possessed outstanding thermoplasticity, and facilitated clinic operability and initial mechanical support. The in vitro study suggested that HA/PLCL bone graft degraded in a spatiotemporal model. Micropores were formed on the non-porous surface at the beginning, and interconnected porous structures were gradually generated. Furthermore, HA/PLCL bone grafts exhibited excellent biocompatibility and osteogenic ability as revealed in vitro cell culture and in vivo animal experiments. When applied to rat periodontal bone defects, the HA/PLCL bone graft showed a non-inferior bone regeneration compared to the commercial DBB. This study proposes a potential bone graft for periodontal bone repair with thermoplastic, spatiotemporal degraded, and osteogenic characteristics.

Secondary Rhinaria Contribute to Major Sexual Dimorphism of Antennae in the Aphid Semiaphis heraclei (Takahashi).

Sexual generation is an important generation in the life cycle of host-alternating aphids, and its population size determines the intensity of the peak in the next spring. Although male trapping techniques based on olfactory stimuli have been successfully established in the field, the biological basis of olfactory perception in males is unclear. In this study, we compared the morphology of antennae and the types, sizes, numbers, and distribution of sensilla between males and sexual females in the host-alternating aphid Semiaphis heraclei (Hemiptera: Aphididae). We found that flagellum length differentiation contributed to the majority of the sexual dimorphism of antennae. Most sensillum types or subtypes, including trichoid sensilla subtype I, campaniform sensilla, and primary rhinaria subtypes I and II, were enlarged in males. In addition, males bore more trichoid sensilla subtype I than sexual females. In particular, secondary rhinaria were present in males only and could not be detected in sexual females. These results revealed the structural basis of male olfactory perception. Our findings provide insight into the mechanism underlying chemical communication between sexual aphids and could thus be useful for pest control.

Effects of exogenous melatonin on sugar and organic acid metabolism in early-ripening peach fruits.

To evaluated the effects melatonin (MT) on the sugar and acid metabolism of early-ripening peach fruits, the concentration of 150 µmol/L MT was sprayed on the leaves of peach trees. MT increased the contents of total soluble sugar and sucrose in peach fruits during the whole ripening period, and increased the contents of glucose and sorbitol at the mature stage. During the whole ripening period, MT also increased the activities of sucrose synthase, sucrose phosphate synthase, neutral invertase, and acidic invertase and the relative expression levels of sucrose synthase, sucrose phosphate synthase, neutral invertase, and acidic invertase genes, while decreased the activity of sorbitol oxidase and the relative expression level of sorbitol dehydrogenase to some extent. Moreover, MT decreased the contents of total organic acid, malic acid, and citric acid at mature stage. At mature stage, MT decreased the activities of citrate synthetase and phosphoenolpyruvate carboxylase and the relative expression levels of citrate synthetase and phosphoenolpyruvate carboxylase genes, while increased the relative expression levels of Nicotinamide adenine dinucleotide phosphate (NADP+)-malic enzyme, malate dehydrogenase, and aconitase genes. Therefore, MT promotes the sugar accumulation and organic acid degradation in early-ripening peach fruits.

Chinese Tofu-Inspired Biomimetic Conductive and Transparent Fibers for Biomedical Applications.

Conductive fibers are vital for next-generation wearable and implantable electronics. However, the mismatch of mechanical, electrical, and biological properties between existing conductive fibers and human tissues significantly retards their further development. Here, the concept of neuro-like fibers to meet these aforementioned requirements is proposed. A new wet spinning process is established to continuously produce pure gelatin hydrogel fibers. The key is the controllable and rapid gelation of spinning solutions based on the salting-out effect, which is inspired by the Chinese food tofu. The resultant fibers exhibit neuro-like features of soft-while-strong mechanical properties, high ionic conductivity, and superior biological properties including biodegradability, biocompatibility, and edibility, which are crucial for implanted applications but seldom reported. Furthermore, all-weather suitable neuro-like fibers with excellent anti-freezing and water retention properties are developed by introducing glycerol for wearable applications. The optical fiber, transient electronics, and electronic data glove made of neuro-like fibers profoundly demonstrate their potential in biomedical applications.

Clock-modified mesenchymal stromal cells therapy rescues molecular circadian oscillation and age-related bone loss via miR142-3p/Bmal1/YAP signaling axis.

Age-related bone loss and disease strongly affect the quality of life of the elderly population. Cellular circadian rhythms have been reported to regulate bone aging, and micro RNAs (miRNAs) play crucial posttranscriptional regulatory roles in the peripheral clock network. Proliferation capability, osteogenic lineage commitment, senescence-associated secreted phenotype (SASP) and circadian oscillation of clock genes under osteogenic condition were assessed in bone marrow mesenchymal stromal cells (BMSCs) from young adult and aged adult mice. miRNAs targeting the core clock gene brain and muscle arntl-like protein 1 (Bmal1) were screened and verified in young and old BMSCs with RT-qPCR and Western Blot analysis. ChIP-seq and RNA-seq datasets were mined to define the downstream mechanism and gain- and loss-of-function genetic experiments were performed to confirm the hypothesis. To compare the therapeutic effect of these clock-engineered BMSCs, SASP and osteogenic capability of Bmal1-overexpressing and miR-142-3p-inhibited BMSCs were investigated in vitro and transplanted into bone defects and femur cavities of aged mice. Aged BMSCs displayed an abolished circadian rhythm, impaired self-renewal capability and decreased osteoblast differentiation. miR-142-3p was elevated with aging, which downregulated Bmal1 and diminished the osteogenic potential of BMSCs. In addition, Bmal1 inhibited YAP expression to promote BMSCs osteogenesis, which was independent from the activation of Hippo signaling pathway. Overexpression of Bmal1 or inhibition of miR-142-3p rescued the molecular temporal rhythm and osteoblast differentiation ex vivo. Cell-based circadian therapy showed improved bone formation and higher turnover levels in vivo. This study demonstrates that transcriptional and post-transcriptional level clock-modified BMSCs rescued circadian oscillation and age-related bone loss via miR-142-3p/Bmal1/YAP signaling axis. These data provide promising clinical prospects of circadian-mediated stromal cell-based therapy and bone tissue regeneration.

Nonsurgical treatment of a hyperdivergent skeletal Class III patient with mini-screw-assisted mandibular dentition distalization and flattening of the occlusal plane.

Treatment of hyperdivergent skeletal Class III malocclusion is challenging for orthodontists, and orthognathic-orthodontic treatment is usually required. This report presents the successful nonsurgical treatment of a 20-year-old man who had a skeletal Class III malocclusion with anterior open bite, anterior and posterior crossbite, hyperdivergent growth pattern, steep occlusal plane, early loss of three first molars, and an uncommon convex profile with a retruded chin. An orthodontic camouflage treatment plan was chosen based on the etiology and the patient's complaints. Tooth #37 was extracted. Miniscrews were used for uprighting and intruding of the lower molars, distalization of the lower dentition, and flattening of the occlusal plane. After 34 months of active treatment, Class I relationships, proper anterior overjet and overbite, flat occlusal plane, and an esthetic facial profile were achieved. The results demonstrated that the biomechanics involved in the nonsurgical treatment assisted with miniscrews to distalize the mandibular dentition and flatten the occlusal plane while keeping the mandibular plane stable was effective for treating this hyperdivergent skeletal Class III patient with a convex profile and anterior open bite.

A single-beam of light priming the immune responses and boosting cancer photoimmunotherapy.

Mirroring the rapid clinical performance, immune checkpoint blockade (ICB) leads a remarkable clinical advance in combating cancer, but suffers poor response in most cancers. The low presence of tumor-infiltration lymphocytes and the poor immunogenicity in tumor microenvironment (TME) are the main factors hindering the effectiveness of ICB in the treatment of immunological "cold" tumors. Aiming at boosting immune response via TME modulation, we report a near-infrared laser-guided photoimmuno-strategy in which synergistic phototherapy, immune adjuvant, and ICB are integrated into one versatile nanoporphyrin platform. The prepared nanoporphyrins are self-assembled from purpurin18-lipids and have photodynamic/photothermal and immunomodulatory effects that can be tuned under a single laser irradiation, concomitant with fluorescence or MSOT imaging. In this work, the contributions of each component in the nanoporphyrin platform were specified. In particular, phototherapy-driven in situ tumor cell death provided abundant tumor-associated antigens to initiate immune responses. With the assist of spatiotemporally delivered immune adjuvant, phototherapy potentiated tumor immunogenicity, reprogrammed "cold" tumors into "hot" ones, and sensitized tumors to ICB therapy. Further combined with PD-L1 blockade, the photoimmune-strategy substantially stimulated tumor-specific immune-responses and long-term immunological memory against primary tumor, abscopal tumor as well as metastatic foci. Such single light-primed photoimmunotherapy offers a promising solution to overcome common hurdles in ICB treatment and can potentially be integrated into existing clinical practice.

Correction to "Highly Efficient Water-Soluble Photosensitizer Based on Chlorin: Synthesis, Characterization, and Evaluation for Photodynamic Therapy".

[This corrects the article DOI: 10.1021/acsptsci.1c00004.].

Artemisia argyi water extract promotes selenium uptake of peach seedlings.

Soil in most areas of the world is selenium (Se) deficient, which results a low Se content in agricultural products. To improve the fruit tree Se accumulation, the effects of different Artemisia argyi water extract concentrations (0, 100, 200, 300, and 400-fold dilutions) on the growth and Se accumulation of peach seedlings were studied by a pot experiment. A 300- and 400-fold dilution of A. argyi water extract increased the root and shoot biomass (dry weight), leaf chlorophyll a content, superoxide dismutase (SOD) activity, and peroxidase (POD) activity of peach seedlings, but decreased the leaf chlorophyll a/b. Different A. argyi water extract concentrations had no significant effects on peach leaf chlorophyll a content of peach seedlings, but increased the leaf carotenoid content, catalase (CAT) activity, and soluble protein content. Different A. argyi water extract concentrations increased the total Se, inorganic Se, and organic contents in roots and shoots of peach seedlings to some extent. Furthermore, A. argyi water extract concentration exhibited a linear relationship with the root and shoot total Se contents. Compared with the control, the 100-, 200-, 300-, and 400-fold dilutions of A. argyi water extract increased the shoot total Se content by 18.95%, 31.31%, 39.32%, and 51.59%, respectively. Different A. argyi water extract concentrations also increased the leaf Se metabolism-related enzyme activities of peach seedlings, including the activities of adenosine triphosphate sulfurase (ATPS), adenosine 5'-phosphosulfate reductase (APR), and serine acetyltransferase (SAT), as well as selenocysteine methyltransferase (SMT) to some extent. Moreover, correlation and grey relational analyses revealed the root total Se content, CAT activity, and ATPS activity to be closely associated with the total shoot Se content. Therefore, applying A. argyi water extract can thus promote the growth and Se uptake of peach seedlings, and the future study should focus on the application effects of Se uptake in peach fruits.

lncRNA NEAT1 ameliorates LPS­induced inflammation in MG63 cells by activating autophagy and suppressing the NLRP3 inflammasome.

The mechanisms of inflammation in bone and joint tissue are complex and involve long non­coding RNAs (lncRNAs), which play an important role in this process. The aim of the present study was to screen out differentially expressed genes in human osteoblasts stimulated by inflammation, and to further explore the mechanisms underlying inflammatory responses and the functional activity of human osteoblasts through bioinformatics methods and in vitro experiments. For this purpose, MG63 cells were stimulated with various concentrations of lipopolysaccharide (LPS) for different periods of time to construct an optimal inflammatory model and RNA sequencing was then performed on these cells. The levels of nuclear enriched abundant transcript 1 (NEAT1), various inflammatory factors, Nod­like receptor protein 3 (NLRP3) protein and osteogenesis­related proteins, as well as the levels of cell apoptosis­ and cell cycle­related markers were measured in MG63 cells stimulated with LPS, transfected with NEAT1 overexpression plasmid and treated with bexarotene by western blot analysis, RT­qPCR, immunofluorescence, FISH, TEM and flow cytometry. There were 427 differentially expressed genes in the LPS­stimulated MG63 cells, in which NEAT1 was significantly downregulated. LPS upregulated the expression of inflammatory cytokines and NLRP3, inhibited the expression of autophagy­related and osteogenesis­related proteins, promoted apoptosis and altered the cell cycle, which was partially inhibited by NEAT1 overexpression and promoted by bexarotene. LPS stimulated inflammation in the MG63 cells and inhibited the retinoid X receptor (RXR)­α to downregulate the expression of NEAT1 and decrease levels of autophagy, which promoted the activation of NLRP3 and the release of inflammatory factors, and impaired the functional activity of osteoblasts, thus promoting the development of inflammation.

Highly Efficient Water-Soluble Photosensitizer Based on Chlorin: Synthesis, Characterization, and Evaluation for Photodynamic Therapy.

The clinical applications of many photosensitizers (PSs) are limited because of their poor water solubility, weak tissue penetration, low chemical purity, and severe toxicity in the absence of light. We designed a novel chlorin-based PS (designated as HPS) to achieve fluorescence image-guided photodynamic therapy (PDT) with efficient ROS generation. In addition to its simple fabrication process, HPS has other advantages such as excellent water solubility, strong NIR absorption, and high biocompatibility upon chemical functionalization for enhanced phototherapy. HPS exhibited high photodynamic performance against lung cancer and breast cancer cells by generating a large amount of singlet oxygen (1O2) under 654 nm laser irradiation. HPS accumulated into multiple organelles such as mitochondria and the endoplasmic reticulum and triggered cell apoptosis by laser exposure. In the tumor-bearing mice, in vivo, HPS showed an optimal half-life in circulation and achieved fluorescence-image-guided PDT within the irradiation window, resulting in effective tumor growth inhibition and the prolonged survival of animals. Moreover, the antitumor PDT effect of HPS was close to the clinical trial phase II stage of HPPH even at the low dosage of 0.32 mg/kg (under 75 J/cm2 laser), while the systemic safety of HPS was much higher. In conclusion, HPS is a novel water-soluble chlorin derivative with excellent PDT potential for clinical transformation.

Fish, vitamin D, and flavonoids in relation to renal cell cancer among smokers.

Fish, vitamin D, flavonoids, and flavonoid-containing foods may have cardiovascular benefits and therefore may also reduce the risk of renal cell cancer. Risk was prospectively assessed in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study (1985-2002) cohort (N = 27,111; 15.2 mean person-years of follow-up). At enrollment, demographic, health, and dietary history information was recorded. Individuals who smoked less than 5 cigarettes/day, with chronic renal insufficiency or prior cancer, were excluded. Hazard ratios and 95% confidence intervals from Cox regression were used to compare upper quartiles (quartiles 2-4) with the lowest quartile (quartile 1) of dietary intake. Among 228 cases, risk (quartile 4 vs. quartile 1) was associated with consumption of the flavonoid quercetin (hazard ratio = 0.6, 95% confidence interval: 0.4, 0.9; P(trend) = 0.015) and Baltic herring (hazard ratio = 2.0, 95% confidence interval: 1.4, 3.0; P(trend) < 0.001), with adjustment for age, body mass index, smoking, blood pressure, alcohol use, physical activity, urban residence, and education. In geographically stratified models, the risks associated with herring and total fish intake appeared to be highest in the urban coast region, although the interaction was not statistically significant. These results suggest that the flavonoid quercetin may prevent renal cell cancer among male smokers. The possible risk associated with fish intake warrants further investigation before conclusions may be drawn.