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Abstract The purpose of this study was to investigate the prevalence and relevant factors of nocturia and its impact on sleep quality in university students in Mainland China. A large-scale survey was conducted on 14,000 university students from 3 universities in Henan province, China by using an anonymous questionnaire. The questionnaire collected the information from the past six months. The relationships between the prevalence of nocturia and its relevant factors were evaluated. A total of 13,874 questionnaires were collected and 13,104 qualified for statistical analysis. A total of 659 students suffered from clinically relevant nocturia (CRN) (4.56% in male and 5.34% in female). Both univariate analysis and the logistic stepwise regression model showed that the prevalence of nocturia was significantly related to female, history of enuresis, ease of waking up, urgency, frequency and RUTI (P

Abstract In recent years, the integration of single‐cell multi‐omics data has provided a more comprehensive understanding of cell functions and internal regulatory mechanisms from a non‐single omics perspective, but it still suffers many challenges, such as omics‐variance, sparsity, cell heterogeneity, and confounding factors. As it is known, the cell cycle is regarded as a confounder when analyzing other factors in single‐cell RNA‐seq data, but it is not clear how it will work on the integrated single‐cell multi‐omics data. Here, a cell cycle‐aware network (CCAN) is developed to remove cell cycle effects from the integrated single‐cell multi‐omics data while keeping the cell type‐specific variations. This is the first computational model to study the cell‐cycle effects in the integration of single‐cell multi‐omics data. Validations on several benchmark datasets show the outstanding performance of CCAN in a variety of downstream analyses and applications, including removing cell cycle effects and batch effects of scRNA‐seq datasets from different protocols, integrating paired and unpaired scRNA‐seq and scATAC‐seq data, accurately transferring cell type labels from scRNA‐seq to scATAC‐seq data, and characterizing the differentiation process from hematopoietic stem cells to different lineages in the integration of differentiation data.

Rare-earth ion dopants in solid-state hosts are ideal candidates for quantum communication technologies, such as quantum memories, due to the intrinsic spin–photon interface of the rare-earth ion combined with the integration methods available in the solid state. Erbium-doped cerium oxide (Er:CeO2) is a particularly promising host material platform for such a quantum memory, as it combines the telecom-wavelength (∼1.5μm) 4f–4f transition of erbium, a predicted long electron spin coherence time when embedded in CeO2, and a small lattice mismatch with silicon. In this work, we report on the epitaxial growth of Er:CeO2 thin films on silicon using molecular beam epitaxy, with controlled erbium concentration between 2 and 130 parts per million (ppm). We carry out a detailed microstructural study to verify the CeO2 host structure and characterize the spin and optical properties of the embedded Er3+ ions as a function of doping density. In as-grown Er:CeO2 in the 2–3 ppm regime, we identify an EPR linewidth of 245(1) MHz, an optical inhomogeneous linewidth of 9.5(2) GHz, an optical excited state lifetime of 3.5(1) ms, and a spectral diffusion-limited homogeneous linewidth as narrow as 4.8(3) MHz. We test the annealing of Er:CeO2 films up to 900 °C, which yields narrowing of the inhomogeneous linewidth by 20% and extension of the excited state lifetime by 40%.

Abstract Background Presently, there is no consensus regarding the optimal serum uric acid (SUA) concentration for pediatric patients. Adenoid and tonsillar hypertrophy is considered to be closely associated with pediatric metabolic syndrome and cardiovascular risk and is a common condition in children admitted to the hospital. Therefore, we aimed to evaluate the relationship between SUA and dyslipidemia and propose a reference range for SUA concentration that is associated with a healthy lipid profile in hospitalized children with adenoid and tonsillar hypertrophy. Methods Preoperative data from 4922 children admitted for elective adenoidectomy and/or tonsillectomy surgery due to adenoid and tonsillar hypertrophy were collected. SUA concentrations were scaled to standard deviation (SD), and SUA deviations were expressed as SD from the mean SUA of children without dyslipidemia. Results The mean SUA concentration of the participants was 4.27 ± 1.01 mg/dL, and the prevalence of hyperuricemia was 1.6% when it was defined using an SUA of ≥ 7.0 mg/dL. Participants with dyslipidemia (856, 17.4%) had a higher prevalence of hyperuricemia (3.4% vs. 1.2%, P 1 SD above the mean value of the participants with ortholiposis. Conclusions SUA was independently associated with dyslipidemia in children with adenoid and tonsillar hypertrophy, and an SUA

Abstract This study aimed to investigate the value of high-frequency ultrasound (HFUS) in differentiation of the seronegative rheumatoid arthritis (SNRA) and osteoarthritis (OA) and in the diagnosis of SNRA. 83 patients diagnosed with SNRA (SNRA group) and 40 diagnosed with OA (OA group) who received HFUS were retrospectively analyzed. The grayscale (GS) scores, power Doppler (PD) scores, and bone erosion (BE)scores were recorded, and added up to calculate the total scores of US variables. The correlations of the total scores of US variables with the 28-joint disease activity score (DAS28), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were analyzed. The diagnostic efficacy of the total scores of US variables for SNRA was assessed. In the SNRA group, the detection rate of abnormal US findings in the joints and tendons by GS and PD as well as BE was higher than those in the OA group. There were significant differences between the two groups in GS scores and PD scores of joints and tendons, and BE scores of joints (P 0.05). Among different US variables, the diagnostic value of total PD scores of the joints was the highest for SNRA. HFUS could be used to differentiate SNRA from OA and make a diagnosis of SNRA based on joint and tendon synovial sheath assessment.

Abstract To assess the efficacy of sacral neuromodulation (SNM) for neurogenic bladder (NB), guided by intraoperative three-dimensional imaging of sacral computed tomography (CT) and mobile C-arm fluoroscopy through video-urodynamics examination. We enrolled 52 patients with NB who underwent conservative treatment with poor results between September 2019 and June 2021 and prospectively underwent SNM guided by intraoperative three-dimensional imaging of sacral CT and mobile C-arm fluoroscopy. Video-urodynamics examination, voiding diary, quality of life questionnaire, overactive bladder symptom scale (OABSS) scoring, and bowel dysfunction exam were completed and recorded at baseline, at SNM testing, and at 6-month follow-up phases. Finally, we calculated the conversion rate from period I to period II, as well as the treatment efficiency and the occurrence of adverse events during the testing and follow-up phases. The testing phase of 52 NB patients was 18–60 days, with an average of (29.3 ± 8.0) days. Overall, 38 patients underwent SNM permanent electrode implantation, whose follow-up phase was 3–25 months, with an average of (11.9 ± 6.1) months. Compared with baseline, the voiding times, daily catheterization volume, quality of life score, OABSS score, bowel dysfunction score, maximum detrusor pressure before voiding, and residual urine volume decreased significantly in the testing phase. The daily voiding volume, functional bladder capacity, maximum urine flow rate, bladder compliance, and maximum cystometric capacity increased significantly in the testing phase. Besides, the voiding times, daily catheterization volume, quality of life score, OABSS score, bowel dysfunction score, maximum detrusor pressure before voiding, and residual urine volume decreased further from the testing to follow-up phase. Daily voiding volume, functional bladder capacity, maximum urine flow rate, bladder compliance, and maximum cystometric capacity increased further from testing to follow-up. At baseline, 10 ureteral units had vesicoureteral reflux (VUR), and 9 of them improved in the testing phase. Besides, there was 1 unit that further improved to no reflux during the follow-up phase. At baseline, 10 patients had detrusor overactivity (DO), and 8 of them improved in the testing phase. Besides, 1 patient’s symptoms further improved during the follow-up phase. At baseline, there were 35 patients with detrusor-bladder neck dyssynergia (DBND); 14 (40.0%) of them disappeared during the testing phase. Among 13 cases who had DBND in the testing phase, 6 (46.2%) disappeared during the follow-up phase. Of the 47 patients with detrusor-external sphincter dyssynergia (DESD) at baseline, 8 (17.0%) disappeared during the testing phase. Among 26 cases who had DESD in the testing phase, 6 (23.1%) disappeared during the follow-up phase. The effective rate of this study was 88.5% (46/52), and the conversion rate from phase I to phase II was 73.1% (38/52). Additionally, the efficacy in a short-term follow-up was stable. SNM guided by intraoperative three-dimensional imaging of sacral CT and mobile C-arm fluoroscopy is an effective and safe treatment option for NB in short time follow-up. It would be well improved in the bladder storage function, sphincter synergetic function and emptying efficiency by video-urodynamics examination in this study. Trial registration: Chinese Clinical Trial Registry. ChiCTR2100050290. Registered August 25 2021. http://www.chictr.org.cn/index.aspx .

Abstract To explore the value of ultrasound in the preoperative diagnosis of nonpalpable testis (NPT) in children. A retrospective study of 254 cases with NPT from May 2017 to December 2021. The preoperative ultrasound examination results were compared with the surgical exploration and pathological results. There were 254 cases (312 testes) NPT has got surgery in our centre. The surgical age were from 6 month to 12 years old, the median age was 2.33 years. There were 103 cases (136 testes) diagnosed as intra-abdominal testis (IAT) by preoperative ultrasound, and 80 cases (103 testes) of extra-abdominal testis (EAT), 71 cases (73 testes) of non-viable testis (NVT). There were 102 cases (135 testes) consistented as IAT by the diagnostic laparoscopy, the preoperative ultrasound’s coincidence of IAT was 99.02%. There were 80 cases (103 testes) consistented as EAT by the diagnostic laparoscopy, the preoperative ultrasound’s coincidence rate was100%. There were 62 cases (62 testes) consistented as NVT by the diagnostic laparoscopy, there were 9 cases (11 testes) misdiagnosed, the preoperative ultrasound’s coincidence rate was 84.9%. Ultrasound can provide valuable information for the preoperative diagnosis of children with nonpalpable testicles, and especially good at identifying the EAT and IAT with normal testicular morphology.

Abstract Intercellular adhesion molecule 1 (ICAM-1) related long noncoding RNA (ICR) is on the antisense strand of ICAM-1 and regulates ICAM-1 expression. ICAM-1 is involved in renal tubulointerstitial injury; however, the expression and clinical implication of ICR are not determined in IgA nephropathy (IgAN). We compared renal ICR levels in 337 IgAN patients with those of 89 biopsy controls, and a markedly increased ICR level was observed in IgAN patients. By Cox proportional hazards models, higher levels of renal ICR were independently associated with disease progression event defined as end-stage renal disease or ≥ 40% decline in estimated glomerular filtration rate. Patients in the highest tertile of renal ICR had a 3.5-fold higher risk for disease progression compared with those in the lowest tertile. The addition of renal ICR to a model with traditional risk factors improved risk prediction of disease progression (net reclassification index: 0.31 [95% CI 0.01–0.50]; integrated discrimination index: 0.10 [95% CI 0.04–0.16]). Inhibition of ICR by transfection with plasmids containing ICR shRNA significantly reduced expression of collagen I and α-SMA, and phosphorylation of Akt and mTOR in TGF-β1- treated HK-2 cells. Our findings suggest that renal ICR might be an independent predictor of IgAN progression and contribute to renal fibrosis.

Exploration of metastable phases of a given elemental composition is a data-intensive task. Here the authors integrate first-principles atomistic simulations with machine learning and high-performance computing to allow a rapid exploration of the metastable phases of carbon.

Mechanical integrity issues are one of the main causes of limited long-term cycle stability for Ni-rich cathode materials. Here the authors analyse the roles of cobalt and manganese and utilise a concentration gradient design to mitigate these issues.

PurposeTo establish a predictive model for upper urinary tract damage (UUTD) in children with neurogenic bladder (NB) and verify its efficacy.MethodsA retrospective study was conducted that consisted of a training cohort with 167 NB patients and a validation cohort with 100 NB children. The clinical data of the two groups were compared first, and then univariate and multivariate logistic regression analyses were performed on the training cohort to identify predictors and develop the nomogram. The accuracy and clinical usefulness of the nomogram were verified by receiver operating characteristic (ROC) curve, calibration curve and decision curve analyses.ResultsThere were no significant differences in other parameters between the training and validation cohorts except for age (all P > 0.05). Recurrent urinary tract infection, bladder compliance, detrusor leak point pressure, overactive bladder and clean intermittent catheterization were identified as predictors and assembled into the nomogram. The nomogram showed good discrimination with the area under the ROC curve (AUC) in the training cohort (0.806, 95% CI: 0.737–0.874) and validation cohort (0.831, 95% CI: 0.753–0.0.909). The calibration curve showed that the nomograms were well calibrated, with no significant difference between the predicted and observed probabilities. Decision curve analysis indicated that the nomogram has good clinical applicability.ConclusionThis study presents an effective nomogram incorporating five clinical characteristics that can be conveniently applied to assess NB children' risk of progressing to UUTD.

ObjectiveThe study aimed to investigate the diagnostic value of ultrasound in children’s transverse testicular ectopia (TTE).Materials and methodsWe retrospectively studies all TTE cases diagnosed in our hospital from January 2017 to December 2021. All cases were evaluated by ultrasound examination and compared to physical examination and diagnostic laparoscopy results.ResultsThis study included 14 TTE patients in total, with a median age was 1.08 years. In the 14 TTE, physical examination found 10 TTE cases, of which nine testes were located in the opposite scrotum, one testis was located in the opposite groin, and the other four testes were not observed by physical examination. All cases were diagnosed by preoperative ultrasound, and nine testes were located in the opposite scrotum, two testes were located in the opposite groin, and three testes were located next to the opposite iliac vessel in the abdominal cavity. Preoperative ultrasound showed the ectopic spermatic cord in six cases (6/14, 42.8%) and persistent Müllerian duct syndrome (PMDS) in one case (1/14, 7%). Diagnostic laparoscopy finally confirmed 14 cases of TTE, which was consistent with preoperative ultrasound, and the coincidence rate was 100% (14/14). Among the 14 cases of TTE, diagnostic laparoscopy showed that 12 cases had ectopic spermatic vessels and vas deferens (12/14, 85.7%), and six cases were associated with PMDS (6/14, 42.8%). When TTE was associated with the ectopic spermatic cord and PMDS, the diagnostic performance of diagnostic laparoscopy was better than that of preoperative ultrasound (P < 0.05). The testis volume of the affected side of TTE was less than that of the contralateral testis (P < 0.05).ConclusionUltrasonography is very helpful for the preoperative diagnosis of TTE in children, and it is suitable as a non-surgical method for locating ectopictestis. Preoperative assessment of the exact presence of PMDS is difficult and unclear. This may be related to factors such as pelvic developmental stages in infancy, examination techniques, and atypical imaging findings of PMDS.

Abstract Magnesium oxide was found to have high‐phosphate‐affinity as an effective component to enhance the phosphate removal ability of common adsorbent materials. However, the currently prepared MgO‐based hybrid adsorbents by conventional methods still suffer from the limited low loading of MgO and inferior removal performances, much far away from practical application. In this study, an ingenious carbon coated MgO nanocomposite is designed by directly burning magnesium in CO2, a well‐known textbook reaction. X‐ray diffraction analysis, scanning electron microscope and aberration‐corrected high‐resolution transmission electron microscope demonstrate the sample is well prepared. Consequently, the high content of nanosized MgO combined with defect‐rich carbon layer brings unprecedented phosphate removal capacity of 1135.0 mg/g, removal rate of 99% and benign compatibility with coexisting anions and solution pH. Furthermore, the removal mechanism is also investigated in detail by characterizing the sample before and after adsorption.

Durability of catalysts under fuel cell reaction conditions is challenging for active nanoalloy electrocatalysts derived from platinum group metals and other transition metals. Here, the authors show that realloying in certain multimetallic nanoalloys plays a major role in enabling the high durability.

Abstract Background Accumulating evidence have highlighted the importance of long noncoding RNAs (lncRNAs) in multiple cancers development and progression. Cancer susceptibility candidate 9 (CASC9) is a novel long non-coding RNA and plays important regulatory role in diverse biological processes of cancers. However, the clinical significance and molecular mechanism of CASC9 in bladder cancer is still unknown. Methods Comprehensive lncRNAs profiling analysis were conducted to identify lncRNAs profile alterations and uncover valuable lncRNA candidates for bladder cancer. The expression level of CASC9 was determined in a total of 106 patients with bladder cancer. Loss-of-function experiments were performed to identify the functions of CASC9 in tumor growth and metastasis of bladder cancer in vitro and in vivo. Bioinformatics analysis and further experiments were performed to explore the molecular mechanisms underlying the functions of CASC9. Results This study found that CASC9 expression was markedly upregulated in bladder cancer and related to histological grade, TNM stage and prognosis. Knockdown of CASC9 inhibited tumor growth and metastasis of bladder cancer in vitro and in vivo. Mechanistically, we found that CASC9 functions as a miRNA sponge to positively regulate FZD6 expression and subsequently activates Wnt/β-catenin signaling pathway, thus playing an oncogenic role in bladder cancer pathogenesis. Conclusion In summary, lncRNA CASC9 plays a critical regulatory role in bladder cancer. The CASC9/miR-497-5p/ FZD6 axis provides insights for regulatory mechanism of bladder cancer, and new strategies for clinical practice.

While metallic glasses are expected to have tunable structures, these have rarely been demonstrated. Here, the authors combine temperature and pressure to show a two-way structural tuning in rare earth-based metallic glasses beyond the nearest-neighbor atomic shells.

To unlock the potential of Mn-based cathode materials, the fast capacity fading process has to be first understood. Here the authors utilize advanced characterization techniques to look at a spinel LiMn2O4 system, revealing that a combination of irreversible structural transformations and Mn dissolution takes responsibility.

Abstract Background To investigate the prognostic risk factors and postoperative recurrence of bladder cancer in patients with upper urinary tract urothelial carcinomas (UTUCs). Methods Data of 439 UTUC patients were retrospectively analyzed. Follow-up and analysis of smoking effects, consumption of traditional Chinese medicine containing aristolochic acid, history of bladder cancer, age, sex, presence or absence of diabetes mellitus (DM), metformin use, tumor characteristics (number, location, stage, grade), and open or laparoscopic surgery on the prognosis of UTUCs were performed. Cox proportional hazard regression analysis was performed to analyze the relationship between various factors and the postoperative survival rate. The survival rate was analyzed using the Kaplan-Meier method. Moreover, logistic regression analysis was performed to analyze the relationship between the above mentioned factors and postoperative recurrence of bladder cancer. Results Overall, 439 patients met, including 236 males (53.7%) and 203 females (46.3%), the criteria for the final statistical analysis, and the average age was 66.7 years. The 1-, 3-, and 5-year overall survival rates of 439 UTUC patients were 90.0, 76.4, and 67.7%, respectively. The 5-year survival rates of T1, T2, T3, and T4 patients were 90.2%, 78%, 43.8%, and 18.5%, respectively. Factors influencing the long-term survival rate of UTUC patients were smoking, taking traditional Chinese medicine containing aristolochic acid, history of bladder cancer, age, tumor size, tumor stage, tumor grade, and lymph node metastasis. The risk factors related to postoperative bladder cancer recurrence were advanced tumor stage, high grade tumor, preoperative ureteroscopy, ureteral urothelial carcinoma, no postoperative bladder perfusion chemotherapy and DM without metformin use. Conclusions Advanced tumor stage and presence of a high-grade tumor were risk factors for not only poor UTUC prognosis but also BC recurrence. In addition, preoperative ureteroscopy, ureteral urothelial carcinoma and DM without metformin use were high risk factors for BC recurrence, whereas regular postoperative bladder perfusion chemotherapy was a protective factor.

Rare-earth ions (REIs) have incomplete 4f shells and possess narrow optical intra-4f transitions due to shielding from electrons in the 5s and 5p orbitals, making them good candidates for solid-state optical quantum memory. The emission of Er3+ in the telecom C-band (1530 nm–1565 nm) makes it especially attractive for this application. In order to build practical, scalable devices, the REI needs to be embedded in a non-interacting host material, preferably one that can be integrated with silicon. In this paper, we show that Er3+ can be isovalently incorporated into epitaxial Y2O3 thin films on Si (111). We report on the synthesis of epitaxial, single-crystalline Er:Y2O3 on Si with a narrow inhomogeneous linewidth in the photoluminescence (PL) spectra, 5.1 GHz (

The triggering mechanism of deep seismicity in Tibet remains unclear. Here the authors use experiments to show that granulite when deformed becomes brittle as it passes into the ecologite stability field developing macroscopic riedel fault zones thus providing an explanation for deep seismicity in Southern Tibet.

Effective band-gap engineering of armchair graphene nanoribbons calls for control over both width and edge structure. Here, the authors report a modular synthesis of narrow N = 6 armchair graphene nanoribbons whose edges can be unsymmetrically modified with heteroarenes, introducing a simple way to tune band gap.

Diamond’s properties are dictated by its crystalline, fully tetrahedrally bonded structure. Here authors synthesize a bulk sp 3-bonded amorphous form of carbon under high pressure and temperature, show that it has bulk modulus comparable to crystalline diamond and that it can be recovered under ambient conditions.

Abstract A multicenter prospective surveillance on dialysis events was carried in 33 dialysis centers in China. Maintenance hemodialysis (HD) outpatients who were dialyzed on the first two days of each month during 2014 were monitored for dialysis events and other infections. During the one-year period, 52,680 patient-months were monitored. Fistula and tunneled or non-tunneled central line were used for 73.70%, 15.70% and 8.85% of vascular access, respectively. There were 773 dialysis events occurred in 671 patients including 589 IV antimicrobial starts, 74 positive blood cultures and 110 local access site infections (LASI). The incidence of dialysis events was 1.47 per 100 patient-months. Among the 74 cases with bloodstream infection (BSI), 38 were access-related BSI (ARB) and there were therefore 148 cases with vascular-related infection (VAI; 38 ARB and 110 LASI). There were 740 cases (1.40 per 100 patient-months) with infections other than BSI and LASI, most (79.19%) of which were respiratory tract infections. For those with dialysis events, there were 425 cases (425/671, 63.34%) admitted to hospital and 12 cases of death (12/671, 1.79%). In conclusion, the surveillance revealed a relatively low incidence of dialysis events and the surveillance may be tailored to target those using central lines in resource-limited settings.

In this approach, a new voltammetric method for determination of norfloxacin was proposed with high sensitivity and wider detection linear range. The used voltammetric sensor was fabricated simply by coating a layer of graphene oxide (GO) and Nafion composited film on glassy carbon electrode. The advantage of proposed method was sensitive electrochemical response for norfloxacin, which was attributed to the excellent electrical conductivity of GO and the accumulating function of Nafion under optimum experimental conditions, the present method revealed a good linear response for determination of norfloxacin in the range of 1×10-8mol/L-7×10-6 mol/L with a detection limit of 5×10-9 mol/L. The proposed method was successfully applied in the determination of norfloxacin in capsules with satisfactory results.

Hepatocellular carcinoma (HCC) is the third leading cause of death due to cancer worldwide with over 500,000 people affected annually. Although chemotherapy has been widely used to treat patients with HCC, alternate modalities to specifically deliver therapeutic cargos to cancer cells have been sought in recent years due to the severe side effects of chemotherapy. In this respect, aptamer-based tumor targeted drug delivery has emerged as a promising approach to increase the efficacy of chemotherapy and reduce or eliminate drug toxicity. In this study, we developed a new HepG2-specific aptamer (HCA#3) by a procedure known as systematic evolution of ligands by exponential enrichment (SELEX) and exploited its role as a targeting ligand to deliver doxorubicin (Dox) to HepG2 cells in vitro. The selected 76-base nucleotide aptamer preferentially bound to HepG2 hepatocellular carcinoma cells but not to control cells. The aptamer HCA#3 was modified with paired CG repeats at the 5'-end to carry and deliver a high payload of intercalated Dox molecules at the CG sites. Four Dox molecules (mol/mol) were fully intercalated in each conjugate aptamer-Dox (ApDC) molecule. Biostability analysis showed that the ApDC molecules are stable in serum. Functional analysis showed that ApDC specifically targeted and released Dox within HepG2 cells but not in control cells, and treatment with HCA#3 ApDC induced HepG2 cell apoptosis but had minimal effect on control cells. Our study demonstrated that HCA#3 ApDC is a promising aptamer-targeted therapeutic that can specifically deliver and release a high doxorubicin payload in HCC cells.

Multiple myeloma, the second most common hematological cancer, is currently incurable due to refractory disease relapse and development of multiple drug resistance. We and others recently established the biophysical model that myeloma initiating (stem) cells (MICs) trigger the stiffening of their niches via SDF-1/CXCR4 paracrine; The stiffened niches then promote the colonogenesis of MICs and protect them from drug treatment. In this work we examined in silico the pharmaceutical potential of targeting MIC niche stiffness to facilitate cytotoxic chemotherapies. We first established a multi-scale agent-based model using the Markov Chain Monte Carlo approach to recapitulate the niche stiffness centric, pro-oncogenetic positive feedback loop between MICs and myeloma-associated bone marrow stromal cells (MBMSCs), and investigated the effects of such intercellular chemo-physical communications on myeloma development. Then we used AMD3100 (to interrupt the interactions between MICs and their stroma) and Bortezomib (a recently developed novel therapeutic agent) as representative drugs to examine if the biophysical properties of myeloma niches are drugable. Results showed that our model recaptured the key experimental observation that the MBMSCs were more sensitive to SDF-1 secreted by MICs, and provided stiffer niches for these initiating cells and promoted their proliferation and drug resistance. Drug synergism analysis suggested that AMD3100 treatment undermined the capability of MICs to modulate the bone marrow microenvironment, and thus re-sensitized myeloma to Bortezomib treatments. This work is also the first attempt to virtually visualize in 3D the dynamics of the bone marrow stiffness during myeloma development. In summary, we established a multi-scale model to facilitate the translation of the niche-stiffness centric myeloma model as well as experimental observations to possible clinical applications. We concluded that targeting the biophysical properties of stem cell niches is of high clinical potential since it may re-sensitize tumor initiating cells to chemotherapies and reduce risks of cancer relapse.

More and more transcription factors and their motifs have been reported and linked to specific gene expression levels. However, focusing only on transcription is not sufficient for mechanism research. Most genes, especially in eukaryotes, are alternatively spliced to different isoforms. Some of these isoforms increase the biodiversity of proteins. From this viewpoint, transcription and splicing are two of important mechanisms to modulate expression levels of isoforms. To integrate these two kinds of regulation, we built a linear regression model to select a subset of transcription factors and splicing factors for each co-expressed isoforms using least-angle regression approach. Then, we applied this method to investigate the mechanism of myelodysplastic syndromes (MDS), a precursor lesion of acute myeloid leukemia. Results suggested that expression levels of most isoforms were regulated by a set of selected regulatory factors. Some of the detected factors, such as EGR1 and STAT family, are highly correlated with progression of MDS. We discovered that the splicing factor SRSF11 experienced alternative splicing switch, and in turn induced different amino acid sequences between MDS and controls. This splicing switch causes two different splicing mechanisms. Polymerase Chain Reaction experiments also confirmed that one of its isoforms was over-expressed in MDS. We analyzed the regulatory networks constructed from the co-expressed isoforms and their regulatory factors in MDS. Many of these networks were enriched in the herpes simplex infection pathway which involves many splicing factors, and pathways in cancers and acute or chronic myeloid leukemia.

In ABO_{3} perovskites, oxygen octahedron rotations are common structural distortions that can promote large ferroelectricity in BiFeO_{3} with an R3c structure [1] but suppress ferroelectricity in CaTiO_{3} with a Pbnm symmetry [2]. For many CaTiO_{3}-like perovskites, the BiFeO_{3} structure is a metastable phase. Here, we report the stabilization of the highly polar BiFeO_{3}-like phase of CaTiO_{3} in a BaTiO_{3}/CaTiO_{3} superlattice grown on a SrTiO_{3} substrate. The stabilization is realized by a reconstruction of oxygen octahedron rotations at the interface from the pattern of nonpolar bulk CaTiO_{3} to a different pattern that is characteristic of a BiFeO_{3} phase. The reconstruction is interpreted through a combination of amplitude-contrast sub-0.1-nm high-resolution transmission electron microscopy and first-principles theories of the structure, energetics, and polarization of the superlattice and its constituents. We further predict a number of new artificial ferroelectric materials demonstrating that nonpolar perovskites can be turned into ferroelectrics via this interface mechanism. Therefore, a large number of perovskites with the CaTiO_{3} structure type, which include many magnetic representatives, are now good candidates as novel highly polar multiferroic materials [3].

Nuclear factor κB (NFκB) activation plays a crucial role in anti-apoptotic responses in response to the apoptotic signaling during tumor necrosis factor (TNFα) stimulation in Multiple Myeloma (MM). Although several drugs have been found effective for the treatment of MM by mainly inhibiting NFκB pathway, there are not any quantitative or qualitative results of comparison assessment on inhibition effect between different drugs either used alone or in combinations. Computational modeling is becoming increasingly indispensable for applied biological research mainly because it can provide strong quantitative predicting power. In this study, a novel computational pathway modeling approach is employed to comparably assess the inhibition effects of specific drugs used alone or in combinations on the NFκB pathway in MM and to predict the potential synergistic drug combinations.

The performance and life of Li-ion battery cathode materials are determined by both the composition (crystal structure and transition metal ratio) and the morphology (particle size, size distribution, and surface area). Careful control of these two aspects is the key to long lasting, high-energy batteries that can undergo fast charge. Developing such cathodes requires manipulation of the synthesis conditions, namely the coprecipitation process to develop the precursor and a calcination step to lithiate and convert it to a transition metal oxide. In this paper, we utilize a combination of controlled synthesis, microscopic and spectroscopic characterization, and multi-scale mathematical modeling to shed light on the synthesis of cathode precursors. The complex interplay between the various chemical reactions in the co-precipitation process is studied to provide experimentalists with guidance on achieving composition control during synthesis. Further, the formation of a variety of morphologies of the primary particles and the driving force for agglomeration is mathematically described, for the first time, based on an energy minimization approach. Results suggest that the presence of Ni and/or Co significantly lowers the reaction rate constant compared to Mn, resulting in agglomerated growth in the former and single crystal growth in the latter. Modeling studies are used to provide a phase map describing the synthesis conditions needed to control the secondary particle size and corresponding size distribution. This paper represents an important step in developing a computationally guided approach to the synthesis of battery cathode materials. [ABSTRACT FROM AUTHOR]

Premelting of ice, a quasi-liquid layer (QLL) at the surface below the melting temperature, was first postulated by Michael Faraday 160 y ago. Since then, it has been extensively studied theoretically and experimentally through many techniques. Existing work has been performed predominantly on hexagonal ice, at conditions close to the triple point. Whether the same phenomenon can persist at much lower pressure and temperature, where stacking disordered ice sublimates directly into water vapor, remains unclear. Herein, we report direct observations of surface premelting on ice nanocrystals below the sublimation temperature using transmission electron microscopy (TEM). Similar to what has been reported on hexagonal ice, a QLL is found at the solid-vapor interface. It preferentially decorates certain facets, and its thickness increases as the phase transition temperature is approached. In situ TEM reveals strong diffusion of the QLL, while electron energy loss spectroscopy confirms its amorphous nature. More significantly, the premelting observed in this work is thought to be related to the metastable low-density ultraviscous water, instead of ambient liquid water as in the case of hexagonal ice. This opens a route to understand premelting and grassy liquid state, far away from the normal water triple point. [ABSTRACT FROM AUTHOR]