A High Rate and Stable Hybrid Li/Na-Ion Battery Based on a Hydrated Molten Inorganic Salt Electrolyte.

Taking into the consideration safety, environmental impact, and economic issue, the construction of aqueous batteries based on aqueous electrolyte has become an indispensable technical option for large-scale electrical energy storage. The narrow electrochemical window is the main problem of conventional aqueous electrolyte. Here, an economical room-temperature inorganic hydrated molten salt (RTMS) electrolyte with a large electrochemical stability window of 3.1 V is proposed. Compared with organic fluorinated molten salts, RTMS is composed of lithium nitrate hydrate and sodium nitrate with much lower cost. Based on the RTMS electrolyte, a hybrid Li/Na-ion full battery is fabricated from cobalt hexacyanoferrate cathode (NaCoHCF) and perylene-3,4,9,10-tetracarboxylic dianhydride (PTCDA) anode. The full cell with the RTMS electrolyte exhibits a fantastic performance with high capacity of 139 mAh g-1 at 1 C, 90 mAh g-1 at 20 C, and capacity retention of 94.7% over 500 cycles at 3 C. The excellent performances are contributed to the unique properties of RTMS with a large electrochemical window, solvated H2 O free and high mobility of Li+ , which exhibits excellent Li-ions insertion and extraction capacity of NaCoHCF. This RTMS cell provides a new economic choice for large-scale energy storage.

Steep Switching of In0.18Al0.82N/AlN/GaN MIS-HEMT (Metal Insulator Semiconductor High Electron Mobility Transistors) on Si for Sensor Applications †.

InAlN/Al/GaN high electron mobility transistors (HEMTs) directly on Si with dynamic threshold voltage for steep subthreshold slope (<60 mV/dec) are demonstrated in this study, and attributed to displacement charge transition effects. The material analysis with High-Resolution X-ray Diffraction (HR-XRD) and the relaxation by reciprocal space mapping (RSM) are performed to confirm indium barrier composition and epitaxy quality. The proposed InAlN barrier HEMTs exhibits high ON/OFF ratio with seven magnitudes and a steep threshold swing (SS) is also obtained with SS = 99 mV/dec for forward sweep and SS = 28 mV/dec for reverse sweep. For GaN-based HEMT directly on Si, this study displays outstanding performance with high ON/OFF ratio and SS < 60 mV/dec behaviors.

Nickel-catalyzed γ-alkylation of cyclopropyl ketones with unactivated primary alkyl chlorides: balancing reactivity and selectivity via halide exchange.

A novel method was developed for synthesizing γ-alkyl ketones via nickel-catalyzed cross-electrophile coupling of cyclopropyl ketones and non-activated primary alkyl chlorides. High reactivity and selectivity can be achieved with sodium iodide as a crucial cocatalyst that generates a low concentration of alkyl iodide via halide exchange, thus avoiding the formation of alkyl dimers. This reaction possessed excellent regioselectivity and high step economy circumventing in situ or pregenerated organometallics.

A Dual-Adjuvanted Parenteral-Intranasal Subunit Nanovaccine generates Robust Systemic and Mucosal Immunity Against SARS-CoV-2 in Mice.

Existing parenteral SARS-CoV-2 vaccines produce only limited mucosal responses, essential for reducing transmission and achieving sterilizing immunity. Appropriately designed mucosal boosters can overcome the shortcomings of parenteral vaccines and enhance pre-existing systemic immunity. Here, a new protein subunit nanovaccine is developed by utilizing dual-adjuvanted (RIG-I: PUUC RNA and TLR-9: CpG DNA) polysaccharide-amino acid-lipid nanoparticles (PAL-NPs) along with SARS-CoV-2 S1 trimer protein, that can be delivered both intramuscularly (IM) and intranasally (IN) to generate balanced mucosal-systemic SARS-CoV-2 immunity. Mice receiving IM-Prime PUUC+CpG PAL subunit nanovaccine, followed by an IN-Boost, developed high levels of IgA, IgG, and cellular immunity in the lungs and showed robust systemic humoral immunity. Interestingly, as a purely intranasal subunit vaccine (IN-Prime/IN-Boost), PUUC+CpG PAL-NPs induced stronger lung-specific T cell immunity than IM-Prime/IN-Boost, and a comparable IgA and neutralizing antibodies, although with a lower systemic antibody response, indicating that a fully mucosal delivery route for SARS-CoV-2 vaccination may also be feasible. The data suggest that PUUC+CpG PAL subunit nanovaccine is a promising candidate for generating SARS-CoV-2 specific mucosal immunity.

A Systematic Review and Meta-analysis of SNOT-22 Outcomes After Sinus Surgery.

Background: All stakeholders in the healthcare system have prioritized and will continue to prioritize enhancing care quality. The measurement of sinus-specific quality of life (QOL) is potentially the most commonly used QOL parameter for chronic rhinosinusitis (CRS). Objective: A systematic review and meta-analysis were used in this study to determine the mean change in patients' scores on the 22-item Sino-Nasal Outcome Test (SNOT-22) before and after endoscopic sinus surgery (ESS) for CRS. Methods: PubMed, Google Scholar, and ScienceDirect were searched for articles that compared SNOT-22 scores before and after ESS in adult patients with CRS and were published between January 2000 and March 2023. The mean post-op change, 95% confidence interval (CI), forest plot, and inverse variance weighting were all generated using a random effects model. A mixed-effects meta-regression was used to analyze the effect of patient-specific characteristics across studies. Results: Fifteen prospective patient cohorts published from 2009 to 2023 were included in this meta-analysis. At an average follow-up of 25.5 months, all studies demonstrated a statistically significant difference in mean SNOT-22 scores between baseline and post-op time periods (P < .05), ranging from 5.1 to 55.4. Across all studies, the mean SNOT-22 changed significantly by 26.02 (95% CI: 12.83-38.60). According to a stepwise multivariate analysis, studies with higher mean age and mean pre-op SNOT-22 scores had greater changes in SNOT-22 scores following ESS, whereas trials with longer mean follow-up duration had smaller changes in SNOT-22 scores. Conclusion: Research utilizing the SNOT-22 instrument has demonstrated that endoscopic sinus surgery (ESS) leads to enhanced quality of life (QOL) outcomes. The literature reports that improvement is influenced by the initial SNOT-22 score, the mean age of the patients, and the duration of the follow-up period.

The Sino-Nasal Outcome Test-22 (SNOT-22) has shown that the quality-of-life results of sinus surgery after endoscopic sinus surgery (ESS) improve significantly. The amount of change seems to vary a lot from one study to the next, and this difference seems to be caused by things like the pre-op SNOT-22 score, the average age of the subjects, and the length of the tracking period. The results of this study give both a single number value and a range of changes that are likely to happen after surgery. These results can be used to guide projects that aim to improve the quality of care. Also, giving the Sino-Nasal Outcome Test-22 (SNOT-22) to people with chronic rhinosinusitis (CRS) before they have surgery may help them understand what effects they can expect, although this is up to each person to decide. Recent preliminary research shows that using SNOT-22 scores and tissue histopathology together could be a new way to predict how well treatment will work for people with CRS. The accuracy and precision of future analyses are likely to get better as efforts are made to get unbiased data and patient-level metrics from a wide range of patients and doctors.

Significance of Nasopharyngeal Cavity Area in Individuals with Adenoid Hypertrophy Assessed by Cone Beam Computed Tomography.

Objective: To determine the significance of the nasopharyngeal cavity area (S) in diagnosing and treating adenoid hypertrophy (AH) in children by measuring it with cone beam computed tomography (CBCT). Methods: A retrospective analysis was conducted on the clinical data of eighty-five 5- to 6-year-old children with AH admitted to the Department of Otorhinolaryngology at Dalian Central Hospital between January 2022 and April 2023. Of the 85 patients, 48 were male and 37 were female; all had been diagnosed with AH and underwent surgery. Sleeping with open-mouth breathing was frequently accompanied by clinical manifestations such as chronic sinusitis in most patients. Every patient was subjected to a CBCT examination of the nasopharynx and 3D airway reconstruction. The adenoid thickness (A) and nasopharyngeal cavity width (N) were measured in the sagittal plane, while the S was measured in the coronal plane. The factors that had a significant impact on S's size was analyzed using linear regression. Results: S and age, A, N, height, weight, BMI, allergic rhinitis, deviated nasal septum, and enlarged turbinate hypertrophy did not differ significantly (P > .05). However, there was a significant linear relationship between A/N and chronic sinusitis (R2 = 0.948, P < .01). Regression equation: S = -4.115 × A/N × 100-5.037 × 1/0 (with chronic sinusitis/without chronic sinusitis) +418. 097. The calculated S in individuals with A/N = 70% and no chronic sinusitis was 130 mm2. Conclusion: The S can be used as an important imaging index for diagnosing and evaluating the severity of AH in minors. When a child exhibits clinical signs of AH but A/N ≤ 70%, it is difficult to determine whether surgical intervention is necessary. At this time, CBCT is required to measure the nasopharyngeal cavity's size. When S ≤ 130 mm2, the patient should actively undertake surgical treatment.

Effects of oral cysteine leukotriene receptor antagonist-montelukast on adenoid lymphoid tissue: a histopathological study under light microscope.

Background: Adenoidal hypertrophy (AH) is one of the most common causes of upper airway obstruction in children. Drug and surgical treatment are the typical treatment of AH. The study on the inflammatory mechanism of AH in children provides a new idea for preoperative intervention and non-surgical treatment with anti-inflammatory drugs such as montelukast sodium (a cysteine leukotriene receptor antagonist). The aim of this study is to evaluate the effect of montelukast sodium on adenoidal lymphoid tissue pathology in children with AH under light microscope. Objective: To study whether there is any change in pathology of the adenoidal lymphoid tissue under the light microscope compared with the control group in children with moderate to severe simple AH treated with montelukast sodium for 1 month before operation. Materials and methods: Twenty patients (8 males, 12 females, 3-8 years old) with moderate to severe AH who were prepared for surgical treatment were selected. All the patients were examined by Nasopharyngeal CT and hemocyte analysis before operation. 20 subjects were randomly divided into two groups: One group was given montelukast chewable tablets 5 mg/d, qn, for 4 weeks; The control group was given placebo 5 mg/d, qn, for 4 weeks. After 4 weeks, the adenoids were removed and examined histopathology. Results: Compared with the control group, the number of lymphocytes in the blood cell analysis of the study group was significantly reduced, with a statistically significant difference (p < 0.05). And the number of germinal centers in adenoid tissue of the study group was relatively reduced, no small cyst was found in the epithelium, and the degree of inflammatory cell infiltration was reduced, with a statistically significant difference (p < 0.05). Conclusion: Montelukast can reduce the number of reactive cells, the number of lymphocytes in blood cells and blood vessels in adenoid lymphoid tissue, which can provide a new idea for preoperative intervention and non-surgical treatment of adenoid hypertrophy in children. However, this is only a pilot study and a longer treatment period is needed to assess the long-term effects of montelukast sodium on adenoid lymphoid tissue. Clinical Trial Registration: www.Chictr.org.cn, identifier ChiCTR2300075040.

A multiadjuvant polysaccharide-amino acid-lipid (PAL) subunit nanovaccine generates robust systemic and lung-specific mucosal immune responses against SARS-CoV-2 in mice.

Existing parenteral SARS-CoV-2 vaccines produce only limited mucosal responses, which are essential for reducing transmission and achieving sterilizing immunity. Appropriately designed mucosal boosters could overcome the shortcomings of parenteral vaccines and enhance pre- existing systemic immunity. Here we present a new protein subunit nanovaccine using multiadjuvanted (e.g. RIG-I: PUUC, TLR9: CpG) polysaccharide-amino acid-lipid nanoparticles (PAL-NPs) that can be delivered both intramuscularly (IM) and intranasally (IN) to generate balanced mucosal-systemic SARS-CoV-2 immunity. Mice receiving IM-Prime PUUC+CpG PAL- NPs, followed by an IN-Boost, developed high levels of IgA, IgG, and cellular immunity in the lung, and showed robust systemic humoral immunity. Interestingly, as a purely intranasal vaccine (IN-Prime/IN-Boost), PUUC+CpG PAL-NPs induced stronger lung-specific T cell immunity than IM-Prime/IN-Boost, and a comparable IgA and neutralizing antibodies, although with a lower systemic antibody response, indicating that a fully mucosal delivery route for SARS-CoV-2 vaccination may also be feasible. Our data suggest that PUUC+CpG PAL-NP subunit vaccine is a promising candidate for generating SARS-CoV-2 specific mucosal immunity.

Higher radiation doses after partial laryngectomy may raise the incidence of pneumonia: A retrospective cohort study.

Background: Currently, studies have shown that a high dose of radiotherapy to the throat have various harmful and adverse effects on the patients' laryngeal function, resulting in the development of pneumonia. This study aimed to explore how radiotherapy dose affected the probability of pneumonia following laryngeal cancer surgery. Materials and methods: A retrospective analysis was done on patients diagnosed with laryngeal cancer between 2010 and 2020 and were treated surgically and with postoperative radiotherapy in the same institution. This study included 108 patients in total, 51 of who were in the low-dose group and 57 of whom were in the high-dose group. Age, gender, the location of laryngeal cancer, the presence or absence of lymph node metastasis, and other demographic and clinical characteristics were collected, and the prevalence of postoperative pneumonia was compared between the two groups. Results: The total prevalence of postoperative pneumonia was 59.3%, but there was a significant difference between the two groups(high-dose group 71.9% VS low-dose group 45.1%; p=0.005). A total of 9.3% (10/108) of the patients had readmission due to severe pneumonia, and the rate of readmission due to pneumonia was significantly different between the two groups (high-dose group 15.8% VS low-dose group 2.0%, p=0.032). Additionally, the high-dose group's prevalence of Dysphagia was significantly higher than the low-dose group's. According to multivariate logistic modeling, high-dose radiation was a risk factor for pneumonia (OR=4.224, 95%CI =1.603-11.131, p=0.004). Conclusion: Pneumonia risk could increase with radiotherapy doses > 50 Gy in the treatment of laryngeal cancer. Therefore, we recommend that when the radiation dose surpasses 50Gy, doctors should pay particular attention to the lung health of patients with laryngeal cancer.

OsCD1 encodes a putative member of the cellulose synthase-like D sub-family and is essential for rice plant architecture and growth.

The cell wall plays important roles in plant architecture and morphogenesis. The cellulose synthase-like super-families were reported to contain glycosyltransferases motif and are required for the biosynthesis of cell wall polysaccharides. Here, we describe a curled leaf and dwarf mutant, cd1, in rice, which exhibits multiple phenotypic traits such as the reduction of plant height and leaf width, curled leaf morphology and a decrease in the number of grains and in the panicle length. Map-based cloning indicates that a member of the cellulose synthase-like D (CSLD) group is a candidate for OsCD1. RNAi transgenic plants with the candidate CSLD gene display a similar phenotype to the cd1 mutant, suggesting that OsCD1 is a member of the CSLD sub-family. Furthermore, sequence analysis indicates that OsCD1 contains the common D,D,D,QXXRW motif, which is a feature of the cellulose synthase-like super-family. Analysis of OsCD1 promoter with GUS fusion expression shows that OsCD1 exhibits higher expression in young meristem tissues such as fresh roots, young panicle and stem apical meristem. Cell wall composition analysis reveals that cellulose content and the level of xylose are significantly reduced in mature culm owing to loss of OsCD1 function. Take together, the work presented here is useful for expanding the understanding of cell wall biosynthesis.

Low-cost flexible plasmonic nanobump metasurfaces for label-free sensing of serum tumor marker.

The use of plasmonic metasurface for sensing has great potential on label-free detection of human tumor markers, which could benefit clinical examination. In this work, we adopt nanoimprint and plasma etching to optimize the nanofabrication for low-cost flexible plasmonic metasurface sensors with gold nanobump arrays, which enable facile surface bio-functionality, high sensitivity and simple optical measurement in the visible range. A high bulk refractive index sensitivity of 454.4 nm/RIU is achieved for the prototype plasmonic metasurface sensors at the wavelengths from 620 nm to 720 nm. The rapid quantitative tumor marker sensing of carcinoembryonic antigen in human serum samples from less than 10 ng/mL to more than 87 ng/mL is achieved, which demonstrates good agreement with the conventional chemiluminescence immunoassay system and sufficiently covers the threshold tumor marker concentration of 20 ng/mL for early cancer prediction. Our method is capable of low-cost high-throughput manufacturing for flexible lightweight plasmonic metasurface sensors, which will facilitate wide applications on portable biomedical sensing devices for future point-of-care diagnosis and mobile healthcare.

Prevalence of Elevated Alanine Aminotransferase by Diagnostic Criterion, Age, and Gender among Adolescents.

BACKGROUND: Serum alanine aminotransferase (ALT) activity was measured not only to detect liver disease, but also to monitor overall health. The purpose of this study was to obtain the prevalence of elevated ALT levels among adolescents. METHODS: In a school-based cross-sectional study, a representative sample was analyzed from 9 middle and high schools in Shenzhen, China, during 2017 to 2018. Elevated ALT was defined as diagnostic criterion I (>30 U/L for boys and >19 U/L for girls) and diagnostic criterion II (>40 U/L). RESULTS: From the adolescent population, a total of 7281 students (boys, 4014, and girls, 3267) aged from 10 to 17 years were collected. The prevalence of elevated ALT was 7.11% (6.88% for boys and 7.41% for girls) by criterion I and 2.72% (3.96% for boys and 1.19% for girls) by criterion II. Based on the Shenzhen census and Chinese national census population, the adjusted prevalence of elevated ALT was 7.65% (boys 7.19% and girls 8.21%) and 6.79% (boys 6.07% and girls 7.56%) by criterion I and 2.85% (boys 4.20% and girls 1.16%) and 2.43% (boys 3.49% and girls 1.29%) by criterion II. For age, the overall trends were increasing progressively, regardless of the use of diagnostic criteria for an elevated ALT activity. CONCLUSIONS: This study supplements the gap that the prevalence of elevated ALT levels differed in gender, age, and criteria among adolescents of Shenzhen. We should take the prevalence as a predictor and continue to play a warning and preventive role in preparation for further intervention.

Photoreceptor Protection by Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF).

Retinal degenerations are a major cause of vision impairment and blindness. Neuroprotective therapy is a promising therapeutic strategy for retinal degenerative diseases. We investigated a novel neurotrophic factor mesencephalic astrocyte-derived neurotrophic factor (MANF) in the retina. MANF is expressed at a high level during postnatal development and the expression declines to a lower level as the retina matures. Müller cells are the major cells expressing MANF. It is also found in the retinal ganglion cells, in the inner nuclear layer (INL) neurons, and in retinal pigment epithelial (RPE) cells. Intravitreal injection of recombinant human (rh)MANF significantly protected rod and cone photoreceptors in rats carrying the rhodopsin S334ter mutation, and preserved electroretinograms (ERGs) in the rd10 (Pde6brd10/rd10 ) mice. These results indicate that MANF is a native protein in the retina and is a potent neurotrophic factor for photoreceptor protection.

Protection of pattern electroretinogram and retinal ganglion cells by oncostatin M after optic nerve injury.

Injury to retinal ganglion cell (RGC) axons leads to selective loss of RGCs and vision. Previous studies have shown that exogenous neurotrophic factors promote RGC survival. We investigated the neuroprotective effects of oncostatin M (OSM), a member of the IL-6 family of cytokines, on pattern electroretinogram (PERG) and RGC survival after optic nerve crush (ON-crush) in the mouse. BALB/C mice received ON-crush in the left eyes for either 4-second or 1-second duration (4-s or 1-s). Fluoro-gold retrograde labeling was used to identify RGCs. RGC function was assessed by PERG measurement. OSM or CNTF protein was injected intravitreally immediately after ON-crush. OSM responsive cells were identified by localization of increased STAT3 phosphorylation. Significant higher RGC survival (46% of untreated control) was seen in OSM-treated eyes when assessed 2 weeks after 4-s ON-crush as compared to that (14% of untreated control) of the PBS-treated eyes (P<0.001). In addition, PERG amplitude was significantly higher in eyes treated with OSM or CNTF 1 week after 1-s ON-crush (36% of baseline) as compared with the amplitude of PBS-treated eyes (19% of the baseline, P = 0.003). An increase in STAT3 phosphorylation was localized in Müller layer after OSM treatment, suggesting that Müller cells mediate the effect of OSM. Our results demonstrate that one single injection of either OSM or CNTF after ON-crush improves RGC survival together with their electrophysiological activity. These data provide proof-of-concept for using neurotrophic factors OSM and CNTF for RGC degenerative diseases, including glaucoma and acute optic nerve trauma.

CCR3 and choroidal neovascularization.

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly in industrialized countries. The "wet" AMD, characterized by the development of choroidal neovacularization (CNV), could result in rapid and severe loss of central vision. The critical role of vascular endothelial growth factor A (VEGF-A) in CNV development has been established and VEGF-A neutralization has become the standard care for wet AMD. Recently, CCR3 was reported to play an important role in CNV development and that CCR3 targeting was reported to be superior to VEGF-A targeting in CNV suppression. We investigated the role of CCR3 in CNV development using the Matrigel induced CNV and found that in both rats and mice, CNV was well-developed in the control eyes as well as in eyes treated with CCR3 antagonist SB328437 or CCR3 neutralizing antibodies. No statistically significant difference in CNV areas was found between the control and SB328437 or CCR3-ab treated eyes. Immunostaining showed no specific expression of CCR3 in or near CNV. In contrast, both VEGF-A neutralizing antibodies and rapamycin significantly suppressed CNV. These results indicate that CCR3 plays no significant role in CNV development and question the therapeutic approach of CCR3 targeting to suppress CNV. On the other hand, our data support the therapeutic strategies of VEGF-A and mTOR (mammalian target of rapamycin) targeting for CNV.

Oncostatin M protects rod and cone photoreceptors and promotes regeneration of cone outer segment in a rat model of retinal degeneration.

Retinitis pigmentosa (RP) is a group of photoreceptor degenerative disorders that lead to loss of vision. Typically, rod photoreceptors degenerate first, resulting in loss of night and peripheral vision. Secondary cone degeneration eventually affects central vision, leading to total blindness. Previous studies have shown that photoreceptors could be protected from degeneration by exogenous neurotrophic factors, including ciliary neurotrophic factor (CNTF), a member of the IL-6 family of cytokines. Using a transgenic rat model of retinal degeneration (the S334-ter rat), we investigated the effects of Oncostatin M (OSM), another member of the IL-6 family of cytokines, on photoreceptor protection. We found that exogenous OSM protects both rod and cone photoreceptors. In addition, OSM promotes regeneration of cone outer segments in early stages of cone degeneration. Further investigation showed that OSM treatment induces STAT3 phosphorylation in Müller cells but not in photoreceptors, suggesting that OSM not directly acts on photoreceptors and that the protective effects of OSM on photoreceptors are mediated by Müller cells. These findings support the therapeutic strategy using members of IL-6 family of cytokines for retinal degenerative disorders. They also provide evidence that activation of the STAT3 pathway in Müller cells promotes photoreceptor survival. Our work highlights the importance of Müller cell-photoreceptor interaction in the retina, which may serve as a model of glia-neuron interaction in general.

Nuclear targeting of cyclin-dependent kinase 2 reveals essential roles of cyclin-dependent kinase 2 localization and cyclin E in vitamin D-mediated growth inhibition.

1,25-Dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)), inhibits proliferation of a variety of cell types including adenocarcinoma of the prostate. We have previously shown that 1,25-(OH)(2)D(3) increases the stability of the cyclin-dependent kinase inhibitor p27(KIP1), decreases cyclin-dependent kinase 2 (CDK2) activity, and promotes G(1) phase accumulation in human prostate cancer cells. These effects correlate with cytoplasmic relocalization of CDK2. In this study, we investigated the role of CDK2 cytoplasmic relocalization in the antiproliferative effects of 1,25-(OH)(2)D(3). CDK2 was found to be necessary for prostate cancer cell proliferation. Although induced by 1,25-(OH)(2)D(3), the cyclin-dependent kinase inhibitor p27(KIP1) was dispensable for 1,25-(OH)(2)D(3)-mediated growth inhibition. Reduction in CDK2 activity by 1,25-(OH)(2)D(3) was associated with decreased T160 phosphorylation, a residue whose phosphorylation in the nucleus is essential for CDK2 activity. Ectopic expression of cyclin E was sufficient to overcome 1,25-(OH)(2)D(3)-mediated cytoplasmic mislocalization of CDK2 and all antiproliferative effects of 1,25-(OH)(2)D(3), yet endogenous levels of cyclin E or binding to CDK2 were not affected by 1,25-(OH)(2)D(3). Similarly, knockdown of the CDK2 substrate retinoblastoma, which causes cyclin E up-regulation, resulted in resistance to 1,25-(OH)(2)D(3)-mediated growth inhibition. Human prostate cancer cells resistant to growth inhibition by 1,25-(OH)(2)D(3) but retaining fully functional vitamin D receptors were developed. These cells did not exhibit 1,25-(OH)(2)D(3)-mediated cytoplasmic relocalization of CDK2. Targeting CDK2 to the nucleus of 1,25-(OH)(2)D(3)-sensitive cancer cells blocked G(1) accumulation and growth inhibition by 1,25-(OH)(2)D(3). These data establish central roles for CDK2 nuclear-cytoplasmic trafficking and cyclin E in the mechanism of 1,25-(OH)(2)D(3)-mediated growth inhibition in prostate cancer cells.