Effects of prenatal cocaine exposure on estrous cycle, and behavior and expression of estrogen receptor alpha and oxytocin during estrus and diestrus in mice offspring.

Increasing evidence indicates that prenatal cocaine exposure may result in many developmental and long-lasting neurological and behavioral effects. The behaviors of female animals are strongly associated with the estrous cycle. Estrogen receptors and oxytocin are important neuroendocrine factors that regulate social behavior and are of special relevance to females. However, whether prenatal cocaine exposure induces estrous cycle changes in offspring and whether neurobehavioral changes in estrus and diestrus offspring differ remains unclear. On gestational day 12, mice were administered cocaine once daily for seven consecutive days, then the estrous cycle was examined in adult female offspring, as well as locomotion, anxiety level, and social behaviors, and the expression of estrogen receptor alpha-immunoreactive and oxytocin-immunoreactive neurons were compared between estrus and diestrus offspring. Prenatal cocaine exposure resulted in the shortening of proestrus and estrus in the offspring. During estrus and diestrus, prenatally cocaine-exposed offspring showed increased anxiety levels and changed partial social behaviors; their motility showed no significant differences in estrus, but declined in diestrus. Prenatal cocaine exposure reduced estrogen receptor alpha-immunoreactive expression in the medial preoptic area, ventromedial hypothalamic nucleus, and arcuate nucleus and oxytocin-immunoreactive expression in the paraventricular nucleus in estrus and diestrus offspring. These results suggest that prenatal cocaine exposure induces changes in the offspring's estrous cycle and expression of estrogen receptor alpha and oxytocin in a brain region-specific manner and that prenatal cocaine exposure and the estrous cycle interactively change motility and partial social behavior. Estrogen receptor alpha and oxytocin signaling are likely to play important concerted roles in mediating the effects of prenatal cocaine exposure on the offspring.

Mechanocatalytic Hydrogen Generation in Centrosymmetric Barium Dititanate.

Novel phase of nano materials that break the traditional structural constraints are highly desirable, particularly in the field of mechanocatalysis, offering versatile applications ranging from energy to medical diagnosis and treatment. In this work, a distinct layered barium dititanate (BaTi2O5) nanocrystals using a pH-modulated hydrothermal method is successfully synthesized. These nanocrystals exhibit outstanding hydrogen generation capability (1160 µmol g-1 h-1 in pure water) and demonstrate remarkable performance in organic dye degradation using ultrasonication. The crystal structure of this newly discovered BaTi2O5 phase, is determined by a combination of synchrotron Powder Diffraction refinement and X-ray adsorption techniques, including X-ray Absorption Near Edge Structure (XANES) and Extended X-ray Absorption Fine Structure (EXAFS). Density Functional Theory calculations revealed that the newly-discovered BaTi2O5 phase demonstrates dipole moments along the z-axis, distributed in an antiparallel direction within a single unit cell. These inherent dipoles induce a surface polarization and a ferroelectric-flexoelectric response under mechanical stimuli when the materials go to nano dimension. With a band alignment well-suitable for hydrogen and reactive oxygen species generation, this BaTi2O5 phase demonstrates promising potential for Mechanocatalysis. The discovery of this distinct phase not only enriches the material candidates for mechanocatalysis but also provides valuable insights.

E-Health Family Interventions for Parents of Children With Autism Aged 0-6 Years: A Scoping Review.

OBJECTIVE: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with onset in infancy. Early intervention is critical to improve the prognosis for these children. E-health interventions have tremendous potential. This review aimed to determine the status and effectiveness of family interventions for parents of children aged 0-6 years with ASD in the context of e-health. METHODS: The review methodology was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. PubMed, Web of Science, and China National Knowledge Infrastructure were searched from inception to June 2022. The searches were limited to children with ASD of the age range between 0 and 6 years. We collated the available information and used descriptive statistics to analyze the synthesized data. RESULTS: Our initial search identified 3,672 articles, of which 30 studies met the inclusion criteria. The 30 articles selected were released between 2012 and 2022. All articles are in English. Most articles reviewed were from high-income countries (27/30, 90.0%), especially from the United States (16/30, 53.3%). Four major themes emerged from the 30 studies that matched the inclusion criteria, as follows: 1) type of e-health interventions, 2) duration of interventions, 3) clinical aspects of e-health interventions, and 4) evidence for intervention effectiveness, looking into the positive, negative, and mixed findings of previous studies. CONCLUSION: These findings suggest that a wide variety of e-health interventions may actually help support both children with ASD aged 0-6 years and their parents.

Model construction and thrombolytic treatment of rat portal vein thrombosis.

OBJECTIVE: To construct a stable rat portal vein thrombosis (PVT) model and explore the time window of urokinase thrombolytic therapy on this basis. METHODS: Constructing a rat PVT model by combining anhydrous ethanol disruption of portal endothelium with stasis of blood flow. Forty-eight rats after PVT modeling were divided into control group and experimental group, with 24 rats in each group. The experimental and control groups were given urokinase treatment and saline tail vein injection, respectively. The two groups of rats were observed and compared for PVT formation at 1, 3 and 5 days after modeling, respectively. RESULTS: A stable rat PVT model was successfully constructed. No significant differences were found in PVT length, portal vein wet weight, and percentage of luminal occlusion area in the control rats at 1, 3, and 5 days after successful modeling (P > 0.05). Compared with control rats 1 day after modeling, the percentage of non-organized thrombus luminal area was significantly decreased (P < 0.0001), and the percentage of organized thrombus luminal area was significantly increased (P < 0.0001) in the PVTs of control rats at 3 and 5 days after modeling. After thrombolytic treatment with urokinase, plasma fibrinogen (FBG) levels were significantly decreased in the experimental group of rats compared with the control group (P < 0.0001), and plasma D-dimer (D2D) levels were significantly increased in the experimental group of rats compared with the control group (P < 0.0001). In addition, we observed prolongation of prothrombin time (PT) in the experimental group at 1, 3 and 5 days after modeling compared to the control group (P = 0.0001). Compared with the control group, portal vein wet weight and PVT length were significantly decreased in the experimental group of rats at 1 day after modeling (P < 0.05), whereas these differences were not found in the two groups of rats at 3 and 5 days after modeling (P > 0.05). The percentage of non-organized thrombus area in the experimental group was significantly decreased compared with that in the control group at 1, 3, and 5 days after modeling (P < 0.05), whereas there was no significant difference in the percentage of lumen area of organized thrombus between the two groups (P > 0.05). CONCLUSION: The method of producing a rat PVT model by destroying the endothelium of the portal vein by anhydrous ethanol combined with blood flow stasis is feasible and reproducible. In addition, the optimal time window for thrombolysis in the treatment of PVT in rats using urokinase is the early stage of thrombosis, when the fibrin content is highest.

Ferroelectrically controlled electromagnetic and transport properties of VN2H2/Al2O3 van der Waals multiferroic heterostructures.

The vertical integration of a ferromagnetic monolayer and a ferroelectric monolayer into van der Waals heterostructures offers a promising route to achieve two-dimensional multiferroic semiconductors owing to the lack of intrinsic single-phase multiferroic materials in nature. In this study, we propose a VN2H2/Al2O3 van der Waals magnetoelectric multiferroic heterostructure and investigate its electronic, magnetic, and transport properties using density functional theory combined with the Boltzmann transport theory. The VN2H2 monolayer is a room-temperature ferromagnetic semiconductor with a band gap of 0.24 eV and a Curie temperature of 411 K, while the Al2O3 monolayer is a ferroelectric semiconductor with a polarization value of 0.11 C m-2. In the VN2H2/Al2O3 van der Waals heterostructures, the conversion between the metal and the semiconductor can be controlled by altering the polarization of the Al2O3 layer. The VN2H2/Al2O3 van der Waals heterostructure retains room-temperature ferromagnetism, and the reverse of polarization is accompanied with a change in the direction of the easy magnetization axis. In addition, electrostatic doping can significantly improve the conductivity of the downward polarization state and transform the upward polarization state from a metal to a half-metal, achieving 100% spin polarization. Our results thus pave the way for achieving highly tunable electromagnetic and transport properties in van der Waals magnetoelectric heterostructures, which have potential applications in next-generation low-power logic and memory devices.

The interaction between TMEM161B (rs768705) and paranoid personality traits in relation to the risk of major depressive disorder: Results form a longitudinal study of 7642 Chinese freshmen.

BACKGROUND: Rs768705 (TMEM161B) is one of the identified single nucleotide polymorphisms related to major depressive disorder (MDD). Paranoid personality traits are independently associated with the risk of MDD. This study aimed to investigate the interaction effect between rs768705 (TMEM161B) and paranoid personality traits on the new-onset risk of MDD in Chinese freshmen. METHODS: A longitudinal study was conducted among 7642 Chinese freshmen without lifetime MDD at baseline in 2018. 158 new-onset MDD cases were ascertained in 2019. DNA samples were extracted to detect the genotype of rs768705. The diagnostic and statistical manual of mental disorders-IV criteria were used to determine MDD and personality disorder traits. Multiplicative interaction was assessed by logistic regression models. Tomas Andersson's method for calculating biological interactions was used to estimate the additive interaction. RESULTS: Rs768705(AG) (OR = 1.88, 95 % CI: 1.24-2.83) and paranoid personality traits (OR = 3.68, 95 % CI: 2.57-5.26) were significantly associated with the risk of MDD. The multiplicative interaction model with the product term of rs768705 and paranoid personality trait traits had a significant interaction effect (OR = 4.20, 95 % CI:1.62-10.91). There was also a significant additive interaction effect (RR = 7.08, 95 % CI:4.31-11.65) for the incidence of MDD. Seventy seven percent patients among new MDD cases were attributed to the additive interaction effect between rs768705 and paranoid personality traits. CONCLUSIONS: Rs768705 (AG) may interact with paranoid personality traits to increase the incidence of MDD among Chinese college students. Schools and psychosocial health organizations should pay more attention to individuals with paranoid personality traits for MDD intervention and prevention.

Association of Estimated Glomerular Filtration Rate Trajectories with Atrial Fibrillation Risk in Populations with Normal or Mildly Impaired Renal Function.

Introduction: The association between the longitudinal patterns of estimated glomerular filtration rate (eGFR) and risk of atrial fibrillation (AF) in populations with normal or mildly impaired renal function is not well characterized. We sought to explore the eGFR trajectories in populations with normal or mildly impaired renal function and their association with AF. Methods: This prospective cohort study included 62,407 participants who were free of AF, cardiovascular diseases, and moderate to severe renal insufficiency (eGFR <60 mL/min/1.73 m2) before 2010. The eGFR trajectories were developed using latent mixture modeling based on examination data in 2006, 2008, and 2010. Incident AF cases were identified in biennial electrocardiogram assessment and a review of medical insurance data and discharge registers. We used Cox regression models to estimate the hazard ratios and 95% confidence intervals (CIs) for incident AF. Results: According to survey results for the range and changing pattern of eGFR during 2006-2010, four trajectories were identified: high-stable (range, 107.47-110.25 mL/min/1.73 m2; n = 11,719), moderate-increasing (median increase from 83.83 to 100.37 mL/min/1.73 m2; n = 22,634), high-decreasing (median decrease from 101.72 to 89.10 mL/min/1.73 m2; n = 7,943), and low-stable (range, 73.48-76.78 mL/min/1.73 m2; n = 20,111). After an average follow-up of 9.63 years, a total of 485 cases of AF were identified. Compared with the high-stable trajectory, the adjusted hazard ratios of AF were 1.70 (95% CI, 1.09-2.66) for the moderate-increasing trajectory, 1.92 (95% CI, 1.18-3.13) for the high-decreasing trajectory, and 2.28 (95% CI, 1.46-3.56) for the low-stable trajectory. The results remained consistent across a number of sensitivity analyses. Conclusion: The trajectories of eGFR were associated with subsequent AF risk in populations with normal or mildly impaired renal function.

The relation between estimated glomerular filtration rate (eGFR) within the normal or mildly impaired range and risk of atrial fibrillation (AF) in former studies is controversial, and data on longitudinal pattern of eGFR in such topic is sparse. In this cohort study, we identified 4 trajectories of eGFR in populations with normal or mildly impaired renal function. Relative to populations with high-stable pattern of eGFR, those with low-stable pattern, high-decreasing pattern and moderate-increasing pattern were associated with 128%, 92%, and 70% higher risk of AF, respectively. These findings suggested that monitoring eGFR trajectories is an important approach for AF prediction in populations with normal or mildly impaired renal function. Decreasing and consistently low eGFR trajectories within the currently designated normal or mildly impaired range may still significantly increase the risk of AF.

Clinical features and outcomes in kidney transplant recipients with COVID-19 pneumonia: a single center retrospective cohort study.

Objective: This retrospective cohort study aimed to assess the clinical features, treatment outcomes, and short-term prognosis in kidney transplant recipients (KTRs) with concurrent coronavirus disease 2019 (COVID-19) pneumonia. Methods: KTRs with COVID-19 pneumonia who were admitted to our hospital from December 28, 2022, to March 28, 2023 were included in the study. Their clinical symptoms, responses to antiviral medications, and short-term prognosis were analyzed. Results: A total of 64 KTRs with initial diagnosis of COVID-19 pneumonia were included in this study. The primary symptoms were fever, cough, and myalgia, with an incidence of 79.7%, 89.1%, and 46.9%, respectively. The administration of antiviral drugs (paxlovid or molnupiravir) within 1-5 days and for over 5 days demonstrated a statistically significant reduction in viral shedding time compared to the group without antiviral medication (P=0.002). Both the paxlovid and molnupiravir treatment groups exhibited a significantly shorter duration of viral shedding time in comparison to the group without antiviral drugs (P=0.002). After 6 months of recovery, there was no significantly negative impact on transplant kidney function (P=0.294). Conclusion: Fever, cough, and myalgia remain common initial symptoms of concurrent COVID-19 pneumonia in KTRs. Early use of antiviral drugs (paxlovid or molnupiravir) is associated with better therapeutic outcomes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had a limited impact on the short-term renal function of the KTRs with concurrent moderate or severe COVID-19 pneumonia.

Enhanced Thermoelectric Performance of N-Type PbSe Through Semi-Coherent Nanostructure by AgCuTe Alloying.

N-type PbSe thermoelectric materials encounter challenges in improving the power factor due to the single-band structure near the Fermi level, which obstructs typical band convergence. The primary strategy for enhancing the thermoelectric figure of merit (ZT) for n-type PbSe involves reducing lattice thermal conductivity (κlat) by introducing various defect structures. However, lattice mismatches resulting from internal defects within the matrix can diminish carrier mobility, thereby affecting electrical transport properties. In this study, n-type AgCuTe-alloyed PbSe systems achieve a peak ZT value of ≈1.5 at 773 K. Transmission electron microscopy reveals nanoprecipitates of Ag2Te, the room temperature second phase of AgCuTe, within the PbSe matrix. Meanwhile, a unique semi-coherent phase boundary is observed between the PbSe matrix and the Ag2Te nanoprecipitates. This semi-coherent phase interface effectively scatters low-frequency phonons while minimizing damage to carrier mobility. Additionally, the dynamic doping effect of Cu atoms from the decomposition of AgCuTe within the matrix further optimize the high-temperature thermoelectric performance. Overall, these factors significantly enhance the ZT across the whole temperature range. The ZT value of ≈1.5 indicates high competitiveness compared to the latest reported n-type PbSe materials, suggesting that these findings hold promise for advancing the development of efficient thermoelectric systems.

Real biofuel and fossil-fuel soot combustion activities in active and passive regeneration of diesel/gasoline particulate filters under different O2/NOx concentrations.

In this work, we aim to investigate and compare the combustion reactivities of real biofuel soot and fossil-fuel soot in the active and passive regeneration conditions of DPF and GPF through temperature-programmed oxidation (TPO). Higher reactivity of biofuel soot is achieved even under GPF conditions with extremely low oxygen concentration (~ 1%), which provides a great potential for low-temperature regeneration of GPF. Such a result is mainly attributed to the low graphitization and less surface C = C groups of biofuel soot. Unfortunately, the presence of high-content ashes (~ 47%) and P impurity in real biofuel soot hinder its combustion reactivity. TPO evidences that the O2/NOX-lacking conditions in GPF are key factors to impact the combustion of soot, especially fossil-fuel soot. This work provides some useful information for understanding real biofuel and fossil-fuel soot combustion in GPF and DPF regeneration and further improvement in filter regeneration process.

Prior to ABOi liver transplant with PD-1 inhibitor in patients with hepatocellular carcinoma: A case report.

BACKGROUND: Liver transplantation (LT) is a unique and effective method for treating end-stage liver diseases and acute liver failure, bringing hope to many patients with liver cancer. LT is currently widely used in the treatment of liver diseases. However, there have been no patients with liver cancer who have undergone ABO-incompatible (ABOi) LT after treatment with the programmed cell death protein 1 (PD-1) inhibitor reported in the literature. CASE PRESENTATION: A patient with liver cancer who received sintilimab injection, an anti-PD1 therapy, before LT was admitted in the transplantation centre. This patient underwent ABOi LT. The perioperative treatment strategy of this patient was reported. A desensitisation protocol was conducted urgently for the patient before operation, and the immunosuppression programme of LT was adjusted. After operation, isoagglutinin titer and liver function indicators were strictly monitored. The patient recovered well after operation, and no sign of rejection reaction was observed. CONCLUSION: We reported a patient with hepatocellular carcinoma (HCC) who received PD-1 inhibitor treatment before operation and successfully underwent ABOi LT. The present case report provides novel insights into the perioperative management of utilizing PD-1 inhibitors prior to ABOi LT in patients diagnosed with hepatocellular carcinoma (HCC).

Engineering Escherichia coli to Efficiently Produce Colanic Acid with Low Molecular Mass and Viscosity.

Colanic acid (CA) is exopolysaccharide that presents growing potential in the food and healthcare industry as a versatile polymer. Previously, we have constructed the Escherichia coli strain WWM16 which can efficiently produce CA. In this study, WWM16 has been further engineered to produce a higher yield of CA with low molecular mass and viscosity. The gene mcbR encoding a transcriptional factor, and the genes opgD, opgG, and opgH related to the biosynthesis of osmoregulated periplasmic glucans were deleted in E. coli WWM16, and the resulting strain WWM166 produced 18.1 g/L CA. The expression level of wcaD encoding the polymerase in WWM166 was downregulated using CRISPRi. As a result, the strain WWM166/pWpD1 could produce 49.9 g/L CA with lower molecular mass. CA products were purified from both WWM166 and WWM166/pWpD1, and their molecular mass, viscosity, fluidity, hygroscopicity, and antioxidant activity were determined and compared. These findings demonstrate the potential application of CA with different molecular masses to prolong life and protect skin in the food and cosmetic industries.

Development and validation of a nomogram to predict poor efficacy of imatinib in the treatment of newly diagnosed chronic phase chronic myeloid leukemia patients.

Background: Imatinib is the most widely used tyrosine kinase inhibitor (TKI) in patients with newly diagnosed chronic-phase chronic myeloid leukemia(CML-CP). However, failure to achieve optimal response after imatinib administration, and subsequent switch to second-generation TKI therapy results in poor efficacy and induces drug resistance. In the present study, we developed and validated a nomogram to predict the efficacy of imatinib in the treatment of patients newly diagnosed with CML-CP in order to help clinicians truly select patients who need 2nd generation TKI during initial therapy and to supplement the risk score system. Methods: We retrospectively analyzed 156 patients newly diagnosed with CML-CP who met the inclusion criteria and were treated with imatinib at the Second Affiliated Hospital of Xi'an Jiao Tong University from January 2012 to June 2022. The patients were divided into a poor-response cohort (N = 60)and an optimal-response cohort (N = 43) based on whether they achieved major molecular remission (MMR) after 12 months of imatinib treatment. Using univariate and multivariate logistic regression analyses, we developed a chronic myeloid leukemia imatinib-poor treatment (CML-IMP) prognostic model using a nomogram considering characteristics like age, sex, HBG, splenic size, and ALP. The CML-IMP model was internally validated and compared with Sokal, Euro, EUTOS, and ELTS scores. Results: The area under the curve of the receiver operator characteristic curve (AUC)of 0.851 (95% CI 0.778-0.925) indicated satisfactory discriminatory ability of the nomogram. The calibration plot shows good consistency between the predicted and actual observations. The net reclassification index (NRI), continuous NRI value, and the integrated discrimination improvement (IDI) showed that the nomogram exhibited superior predictive performance compared to the Sokal, EUTOS, Euro, and ELTS scores (P < 0.05). In addition, the clinical decision curve analysis (DCA) showed that the nomogram was useful for clinical decision-making. In predicting treatment response, only Sokal and CML-IMP risk stratification can effectively predict the cumulative acquisition rates of CCyR, MMR, and DMR (P<0.05). Conclusion: We constructed a nomogram that can be effectively used to predict the efficacy of imatinib in patients with newly diagnosed CML-CP based on a single center, 10-year retrospective cohort study.

Synergy of Oxygen Octahedra Distortion and Polar Nanodomains Induced Emergent Electrocaloric Effect in NaNbO3-Based Ceramics.

High-performance electrocaloric materials are essential for the development of solid-state cooling technologies; however, the contradiction of the electrocaloric effect (ECE) and temperature span in ferroelectrics frustrates practical applications. In this work, through modulating oxygen octahedra distortion and short-range polar nanodomains with moderate coupling strength, an EC value of ΔT ∼ 0.30 K with an ultrawide temperature span of 85 K is obtained in the x = 0.04 composition [(0.88 - x)NaNbO3-0.12BaTiO3-xLiSbO3 (x = 0-0.06)]. The LiSbO3 dopant induces a P4bm-to-R3cH phase transition and intensifies the oxygen octahedra distortion degree, accompanied by the ferroelectric domain smashing into polar nanodomains. Also, LiSbO3 addition enhances the relaxation degree with a downshift of Tfd (ferroelectric-to-diffuse phase transition temperature) and TJ (temperature of the maximal current density value), and Tfd is shifted to near room temperature with an absence of TJ in x = 0.04. Local energy barriers induced by oxygen octahedra distortion inhibit the phase transition in conjunction with activation of short-range polar order switching under thermal stimuli, which is the underlying mechanism for an excellent EC performance for x = 0.04. This work not only clarifies that ferroelectrics with oxygen octahedra distortion and short-range polar order are expected to achieve remarkable EC performances but also provides a design strategy to seek emergent EC behaviors in complex oxygen-octahedra-distortion materials.

Predicting the Population Risk of Suicide Using Routinely Collected Health Administrative Data in Quebec, Canada: Model-Based Synthetic Estimation Study.

BACKGROUND: Suicide is a significant public health issue. Many risk prediction tools have been developed to estimate an individual's risk of suicide. Risk prediction models can go beyond individual risk assessment; one important application of risk prediction models is population health planning. Suicide is a result of the interaction among the risk and protective factors at the individual, health care system, and community levels. Thus, policy and decision makers can play an important role in suicide prevention. However, few prediction models for the population risk of suicide have been developed. OBJECTIVE: This study aims to develop and validate prediction models for the population risk of suicide using health administrative data, considering individual-, health system-, and community-level predictors. METHODS: We used a case-control study design to develop sex-specific risk prediction models for suicide, using the health administrative data in Quebec, Canada. The training data included all suicide cases (n=8899) that occurred from January 1, 2002, to December 31, 2010. The control group was a 1% random sample of living individuals in each year between January 1, 2002, and December 31, 2010 (n=645,590). Logistic regression was used to develop the prediction models based on individual-, health care system-, and community-level predictors. The developed model was converted into synthetic estimation models, which concerted the individual-level predictors into community-level predictors. The synthetic estimation models were directly applied to the validation data from January 1, 2011, to December 31, 2019. We assessed the performance of the synthetic estimation models with four indicators: the agreement between predicted and observed proportions of suicide, mean average error, root mean square error, and the proportion of correctly identified high-risk regions. RESULTS: The sex-specific models based on individual data had good discrimination (male model: C=0.79; female model: C=0.85) and calibration (Brier score for male model 0.01; Brier score for female model 0.005). With the regression-based synthetic models applied in the validation data, the absolute differences between the synthetic risk estimates and observed suicide risk ranged from 0% to 0.001%. The root mean square errors were under 0.2. The synthetic estimation model for males correctly predicted 4 of 5 high-risk regions in 8 years, and the model for females correctly predicted 4 of 5 high-risk regions in 5 years. CONCLUSIONS: Using linked health administrative databases, this study demonstrated the feasibility and the validity of developing prediction models for the population risk of suicide, incorporating individual-, health system-, and community-level variables. Synthetic estimation models built on routinely collected health administrative data can accurately predict the population risk of suicide. This effort can be enhanced by timely access to other critical information at the population level.

The relationship between coffee-related factors and cortical and hippocampal structure: a triangulation of evidence approach and Mendelian randomization research.

Objective: Existing studies have reported sustained changes in the cortical structure of rats due to coffee-related factors, which are speculated to occur in the human body. However, there is a lack of research on this topic. Additionally, previous observational studies have found the impact of diseases on cortical structure and the potential therapeutic effects of coffee on these diseases. Our aim was to study the causal effects of coffee-related factors on the human brain using SNPs (single nucleotide polymorphisms). We will connect these discovered causal effects to the impact of diseases on the brain. Through triangulating evidence, we will reveal the potential active areas of coffee in preventing diseases. Methods: We utilized GWAS data from multiple cohorts and their databases, selecting instrumental variables for genetic prediction of coffee intake and plasma levels of caffeine and its direct metabolites. We applied these instrumental variables to individual data on cortical thickness and surface area, as well as hippocampal volume, from the ENIGMA and CHARGE consortium for Mendelian randomization analysis (MR). Triangular evidence was obtained by integrating existing evidence through a specified retrieval strategy, calculating the overlap between coffee's effects on brain regions and disease-related brain regions to identify potential regions of action. Results: The MR analysis yielded 93 positive results for 9 exposures, among which theobromine, a metabolite in the caffeine pathway, was found to be associated with increased hippocampal volume. For cortical structure, theobromine in the caffeine pathway was associated with a decrease in total surface area, while theobromine and caffeine in the pathway were associated with an increase in total thickness. The overlap rate of triangular evidence showed no difference in both overall and subgroup analyses, indicating a high overlap between the effects of coffee on brain regions and disease. Conclusions: From predicted outcomes from causal effects, coffee intake-related factors may have lasting effects on cortical structure. Additionally, theobromine and theophylline have the greatest impact on certain brain gyri, rather than caffeine. Triangulation evidence indicates that disease and coffee intake-related factors act on the same cortical regions, suggesting the presence of potential shared or antagonistic pathways.

Magnetic Field-induced Disordered Phase of Spinel Oxides for High Battery Performance.

The disordered phase of spinel LiMn1.5Ni0.5O4 (LNMO) is more appealing as high-voltage cathode due to its superior electrochemical performance compared to its ordered counterpart. Various methods are developed to induce a phase transition. However, the resulting materials often suffer from capacity degradation due to the adverse influence of accompanying Mn3+ ions. This study presents the utilization of local magnetic fields generated by a magnetic Fe3O4 shell to induce a disordered phase transition in LNMO at lower temperature, transitioning it from an order state without significantly increasing the Mn3+ content. The pivotal role played by the local magnetic fields is evidenced through comparisons with samples with nonmagnetic Al2O3 shell, samples subjected to sole heat treatment, and samples heat-treated within magnetic fields. The key finding is that magnetic fields can initiate a radical pair mechanism, enabling the induction of order-disorder phase transition even at lower temperatures. The disordered spinal LNMO with a magnetic Fe3O4 shell exhibits excellent cycling stability and kinetic properties in electrochemical characterization as a result. This innovation not only unravels the intricate interplay between the disordered phase and Mn3+ content in the cathode spinel but also pioneers the use of magnetic field effects for manipulating material phases.

The prognostic impact of tumor location in non-muscle-invasive bladder cancer patients undergoing transurethral resection: insights from a cohort study utilizing chinese multicenter and SEER registries.

OBJECTIVE: Most bladder cancers are non-muscle invasive bladder cancer (NMIBC), and transurethral resection of bladder tumors (TURBT) is the standard treatment. However, postoperative recurrence remains a significant challenge, and the influence of bladder tumor location on prognosis is still unclear. This study aims to investigate how tumor location affects the prognosis of NMIBC patients undergoing TURBT and to identify the optimal surgical approach. METHODS: A multicenter study was conducted, which included Chinese NMIBC data from 15 hospitals (1996-2019) and data from 17 registries of the Surveillance, Epidemiology, and End Results database (SEER) (2000-2020). Patients initially diagnosed with NMIBC and undergoing TURBT or partial cystectomy were analyzed, with cases lost to follow-up or with missing data excluded. The study investigated the overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) among patients with different tumor locations. Kaplan-Meier, Cox regression, and propensity score matching methods were employed to explore the association between tumor location and prognosis. Stratified populations were analyzed to minimize bias. RESULTS: This study included 118,477 NMIBC patients and highlighted tumor location as a crucial factor impacting post-TURBT prognosis. Both anterior wall and dome tumors independently predicted adverse outcomes in two cohorts. For anterior wall tumors, the Chinese cohort showed hazard ratios (HR) for OS of 4.35 (P < 0.0001); RFS of 2.21 (P < 0.0001); SEER cohort OS HR of 1.10 (P = 0.0001); DSS HR of 1.13 (P = 0.0183). Dome tumors displayed similar trends (Chinese NMIBC cohort OS HR of 7.91 (P < 0.0001); RFS HR of 2.12 (P < 0.0001); SEER OS HR of 1.05 (P = 0.0087); DSS HR of 1.14 (P = 0.0006)). Partial cystectomy significantly improved the survival of dome tumor patients compared to standard TURBT treatment (P < 0.01). CONCLUSION: This study reveals the significant impact of tumor location in NMIBC patients on the outcomes of TURBT treatment, with tumors in the anterior wall and bladder dome showing poor post-TURBT prognosis. Compared to TURBT treatment, partial cystectomy improves the prognosis for bladder dome tumors. This study provides guidance for personalized treatment and prognosis management for NMIBC patients.

Adhesion between EVs and tumor cells facilitated EV-encapsulated doxorubicin delivery via ICAM1.

Doxorubicin (Dox) is an anti-tumor drug with a broad spectrum, whereas the cardiotoxicity limits its further application. In clinical settings, liposome delivery vehicles are used to reduce Dox cardiotoxicity. Here, we substitute extracellular vesicles (EVs) for liposomes and deeply investigate the mechanism for EV-encapsulated Dox delivery. The results demonstrate that EVs dramatically increase import efficiency and anti-tumor effects of Dox in vitro and in vivo, and the efficiency increase benefits from its unique entry pattern. Dox-loading EVs repeat a "kiss-and-run" motion before EVs internalization. Once EVs touch the cell membrane, Dox disassociates from EVs and directly enters the cytoplasm, leading to higher and faster Dox import than single Dox. This unique entry pattern makes the adhesion between EVs and cell membrane rather than the total amount of EV internalization the key factor for regulating the Dox import. Furthermore, we recognize ICAM1 as the molecule mediating the adhesion between EVs and cell membranes. Interestingly, EV-encapsulated Dox can induce ICAM1 expression by irritating IFN-γ and TNF-α secretion in TME, thereby increasing tumor targeting of Dox-loading EVs. Altogether, EVs and EV-encapsulated Dox synergize via ICAM1, which collectively enhances the curative effects for tumor treatment.

Highly luminescent and stable CsPbBr3 perovskite nanocrystals coated with polyethersulfone for white light-emitting diode applications.

Simultaneously improving the stability and photoluminescence quantum yield (PLQY) of all inorganic perovskite nanocrystals (NCs) is crucial for their practical utilization in various optoelectronic devices. Here, CsPbBr3 NCs coated with polyethersulfone (PES) were prepared via an in-situ co-precipitation method. The sulfone groups in PES bind to undercoordinated lead ion (Pb2+) on the CsPbBr3 NCs, resulting in significant reduction of surface defects, thus enhancing the PLQY from 74.2% to 88.3%. Meanwhile, the PES-coated NCs exhibit high water resistance and excellent heat and light stability, maintaining over 85% of the initial PL intensity under thermal aging (70°C, 4 h) and continuous 365 nm ultraviolet (UV) light irradiation (24 W, 8 h) conditions. By contrast, the PL intensity of the control NCs dramatically dropped to less than 40%. Finally, a diode emitting bright white light was fabricated utilizing the PES-coated CsPbBr3 NCs, which exhibits a color gamut of ~110% NTSC standard.