Molecular Prevalence and Geographical Variations of Carbapenem-Resistant Klebsiella pneumoniae ST15 Isolates in a Tertiary Hospital in Ningbo, China.

BACKGROUND In China, the most prevalent type of CRKP is ST11, but the high-risk clone ST15 has grown in popularity in recent years, posing a serious public health risk. Therefore, we investigated the molecular prevalence characteristics of ST15 CRKP detected in a tertiary hospital in Ningbo to understand the current potential regional risk of ST15 CRKP outbreak. MATERIAL AND METHODS We collected and evaluated 18 non-duplicated CRKP strains of ST15 type for antibiotic resistance. Their integrons, virulence genes, and resistance genes were identified using polymerase chain reaction (PCR), and their homology was determined using MALDI-TOF MS. RESULTS The predominant serotype of 18 ST15 CRKP strains was K5. ST15 CRKP exhibited the lowest antimicrobial resistance to Cefoperazone/sulbactam (11.1%), followed by trimethoprim/sulfamethoxazole (22.2%). Resistance gene testing revealed that 14 out of 18 ST15 CRKP strains (77.8%) carried Klebsiella pneumoniae carbapenemase 2 (KPC-2), whereas all ST15 CRKP integrons were of the intI1 type. Furthermore, virulence gene testing revealed that all 18 ST15 CRKP strains carried ybtS, kfu, irp-1, and fyuA genes, followed by the irp-2 gene (17 strains) and entB (16 strains). The homology analysis report showed that 2 clusters had closer affinity, which was mainly concentrated in classes C and D. CONCLUSIONS The ST15 CRKP antibiotic resistance rates demonstrate clear geographical differences in Ningbo. Additionally, some strains carried highly virulent genes, indicating a possible evolution towards carbapenem-resistant highly virulent strains. To reduce the spread of ST15 CRKP, we must rationalize the clinical use of antibiotics and strengthen resistance monitoring to control nosocomial infections.

Exploring the impact of irradiation on the sensory quality of pork based on a metabolomics approach.

The effects of irradiation on pork quality characteristics were investigated by combining sensory experiments, pork color, TBARS, volatile components, and differential metabolites. Pork irradiated at a dose of 1 kGy received the highest sensory scores, whereas pork irradiated at doses of 3 and 5 kGy obtained lower sensory scores, particularly with regard to odor. Irradiation makes pork more ruddy and promotes fat oxidation, leading to increased a* and TBARS values. The main volatile substances in irradiated pork were hydrocarbons, aldehydes, and alcohols, and hexanal, heptanal, and valeric acid were considered as important substances responsible for the generation of radiation-induced off-flavors. 65 differential metabolites were identified. l-pyroglutamic acid, l-glutamate, l-proline, fumarate acids, betaine, and l-anserine were considered as the main substances contributing to the differences in pork quality. In addition, metabolic pathways such as arginine biosynthesis, alanine, aspartate and glutamate metabolism were found to be considerably affected by irradiation.

Integrative multi-omics profiling in human decedents receiving pig heart xenografts.

In a previous study, heart xenografts from 10-gene-edited pigs transplanted into two human decedents did not show evidence of acute-onset cellular- or antibody-mediated rejection. Here, to better understand the detailed molecular landscape following xenotransplantation, we carried out bulk and single-cell transcriptomics, lipidomics, proteomics and metabolomics on blood samples obtained from the transplanted decedents every 6 h, as well as histological and transcriptomic tissue profiling. We observed substantial early immune responses in peripheral blood mononuclear cells and xenograft tissue obtained from decedent 1 (male), associated with downstream T cell and natural killer cell activity. Longitudinal analyses indicated the presence of ischemia reperfusion injury, exacerbated by inadequate immunosuppression of T cells, consistent with previous findings of perioperative cardiac xenograft dysfunction in pig-to-nonhuman primate studies. Moreover, at 42 h after transplantation, substantial alterations in cellular metabolism and liver-damage pathways occurred, correlating with profound organ-wide physiological dysfunction. By contrast, relatively minor changes in RNA, protein, lipid and metabolism profiles were observed in decedent 2 (female) as compared to decedent 1. Overall, these multi-omics analyses delineate distinct responses to cardiac xenotransplantation in the two human decedents and reveal new insights into early molecular and immune responses after xenotransplantation. These findings may aid in the development of targeted therapeutic approaches to limit ischemia reperfusion injury-related phenotypes and improve outcomes.

Dihydroquercetin alleviates dopamine neuron loss via regulating TREM2 activation.

BACKGROUND: Parkinson's disease (PD) is a prevalent neurodegenerative disorder, marked by the degeneration of dopamine (DA) neurons in the substantia nigra (SN). Current evidence strongly suggests that neuroinflammation, primarily mediated by microglia, contributes to PD pathogenesis. Triggering receptor expressed on myeloid cells 2 (TREM2) might serve as a promising therapeutic target for PD due to its ability to suppress neuroinflammation. Dihydroquercetin (DHQ) is an important natural dihydroflavone and confers apparent anti-inflammatory, antioxidant and anti-fibrotic effects. Recently, DHQ-mediated neuroprotection was exhibited. However, the specific mechanisms of its neuroprotective effects remain incompletely elucidated. METHODS: In this study, rat models were utilized to induce damage to DA neurons using lipopolysaccharide (LPS) and 6-hydroxydopamine (6-OHDA) to assess the impacts of DHQ on the loss of DA neurons. Furthermore, DA neuronal MN9D cells and microglial BV2 cells were employed to investigate the function of TREM2 in DHQ-mediated DA neuroprotection. Finally, TREM2 knockout mice were used to investigate whether the neuroprotective effects mediated by DHQ through a mechanism dependent on TREM2. RESULTS: The main findings demonstrated that DHQ effectively protected DA neurons against neurotoxicity induced by LPS and 6-OHDA and inhibited microglia-elicited neuroinflammation. Meanwhile, DHQ promoted microglial TREM2 signaling activation. Notably, DHQ failed to reduce inflammatory cytokines release and further present neuroprotection from DA neurotoxicity upon TREM2 silencing. Similarly, DHQ didn't exert DA neuroprotection in TREM2 knockout mice. CONCLUSIONS: These findings suggest that DHQ exerted DA neuroprotection by regulating microglia TREM2 activation.

Effect of Chinese quince proanthocyanidins on the inhibition of heterocyclic amines and quality of fried chicken meatballs and tofu.

Heterocyclic amines (HCAs) have potential carcinogenic and mutagenic activity and are generated in cooked protein-rich foods. Adding proanthocyanidins (PAs) to these foods before frying is an effective way to reduce HCAs. In this study, polymeric PAs (PPA) and ultrasound-assisted acid-catalyzed/catechin nucleophilic depolymerized PAs (UAPA, a type of oligomeric PA) were prepared from Chinese quince fruits (CQF). Different levels of PPA and UAPA (0.05%, 0.1%, and 0.15%) were added to chicken meatballs and tofu; then these foods were fried, and the content of HCAs in them after frying was investigated. The results showed that PPA and, particularly, UAPA significantly inhibited the formation of HCAs in fried meatballs and tofu, and this inhibition was dose-dependent. The inhibition of HCAs by both PPA and UAPA was stronger in the chicken meatballs than in fried tofu. The level of total HCAs was significantly reduced by 57.84% (from 11.93 to 5.03 ng/g) after treatment of meatballs with 0.15% UAPA, with inhibition rates of 78.94%, 50.37%, and 17.81% for norharman, harman, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), respectively. Of note, there was a negative correlation between water, lipid, protein, creatine, and glucose content and HCA content in the crust, interior, and whole (crust-plus-interior) measurements of all fried samples. Interestingly, PPA and UAPA were found more effective in inhibiting HCAs in the exterior crust than in the interior of the fried chicken meatballs. These results provide evidence that further studies on the reduction of the formation of harmful HCAs in fried foods by adding CQF PAs could be valuable to the fried food industry. PRACTICAL APPLICATION: Chinese quince proanthocyanidins treatments significantly inhibited the generation of heterocyclic amines (HCAs) in chicken meatballs and tofu when deep-fried. These results suggest that Chinese quince proanthocyanidins can be used as natural food additive for reducing HCAs in fried foods, laying the foundation for using Chinese quince fruit proanthocyanidins for HCA inhibition in the food industry.

A de novo Mutation (p.Gln277X) of Cyclin D2 is Responsible for a Child with Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome.

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH), a type of overgrowth syndrome, is characterized by progressive megalencephaly, cortical brain malformations, and distal limb anomalies. Previous studies have revealed that the overactivity of the phosphatidylinositol 3-kinase-Protein kinase B pathway and the increased cyclin D2 (CCND2) expression were the main factors contributing to this disease. Here, we present the case of a patient who exhibited megalencephaly, polymicrogyria, abnormal neuronal migration, and developmental delay. Serum tandem mass spectrometry and chromosome examination did not detect any metabolic abnormalities or copy number variants. However, whole-exome sequencing and Sanger sequencing revealed a de novo nonsense mutation (NM_001759.3: c.829C>T; p.Gln277X) in the CCND2 gene of the patient. Bioinformatics analysis predicted that this mutation may disrupt the structure and surface charge of the CCND2 protein. This disruption could potentially prevent polyubiquitination of CCND2, leading to its resistance against degradation. Consequently, this could drive cell division and growth by altering the activity of key cell cycle regulatory nodes, ultimately contributing to the development of MPPH. This study not only presents a new case of MPPH and expands the mutation spectrum of CCND2 but also enhances our understanding of the mechanisms connecting CCND2 with overgrowth syndromes.

Superhydrophobic Non-Metallic Surfaces with Multiscale Nano/Micro-Structure: Fabrication and Application.

Multiscale nano/micro-structured surfaces with superhydrophobicity are abundantly observed in nature such as lotus leaves, rose petals and butterfly wings, where microstructures typically reinforce mechanical stability, while nanostructures predominantly govern wettability. To emulate such hierarchical structures in nature, various methods have been widely applied in the past few decades to the manufacture of multiscale structures which can be applied to functionalities ranging from anti-icing and water-oil separation to self-cleaning. In this review, we highlight recent advances in nano/micro-structured superhydrophobic surfaces, with particular focus on non-metallic materials as they are widely used in daily life due to their lightweight, abrasion resistance and ease of processing properties. This review is organized into three sections. First, fabrication methods of multiscale hierarchical structures are introduced with their strengths and weaknesses. Second, four main application areas of anti-icing, water-oil separation, anti-fog and self-cleaning are overviewed by assessing how and why multiscale structures need to be incorporated to carry out their performances. Finally, future directions and challenges for nano/micro-structured surfaces are presented.

Large regions of homozygosity in prenatal diagnosis.

Chromosomal microarrays (CMA) incorporate single nucleotide polymorphisms to enable the detection of regions of homozygosity (ROH). Here, we retrospectively analyzed 6288 prenatal cases who performed CMA to explored the clinical implications of large ROH in prenatal diagnosis. We analyzed cases with ROH larger than 10 megabases and reviewed the ultrasound findings; karyotype results and pregnancy follow-up data. Cases with possible imprinting disorders were assessed by methylation-specific multiplex ligation-dependent probe amplification. In total, we identified 50 cases with large ROH and chromosomes 1 and 2 were the most affected. About 59.18% of the ROH cases had ultrasound abnormalities, with the most common findings being ultrasound soft-marker abnormalities. There were seven fetuses had ROH which covered almost the entire chromosome and four had terminal ROH that involved almost the entire long arm of the chromosomes, which indicated uniparental disomy (UPD), of which 70% showed abnormal ultrasound findings. Ten cases with multiple ROH on different chromosomes indicated the third to fifth degree of consanguinity. In this study, we highlighted the clinical relevance of large ROH related to UPD. The analysis of ROH allowed us to gain further understanding of complex cytogenetic and disease mechanisms in prenatal diagnosis.

Association between sleep duration and serum neurofilament light chain levels among adults in the United States.

Background: Neurofilaments are neuron specific skeleton proteins maintaining axon transduction speed, leaked into cerebrospinal fluid and serum after axonal injury or neuron death. Sleep duration change has long related to many health issues but lack laboratory examination. Methods: This study enrolled total 10,175 participants from 2013 to 2014 National Health and Nutrition Examination Survey and used a multi-variable linear model to analyze the relationship between sleep duration and serum neurofilament light chain (sNfL) level. Results: There was a fixed relationship between sleep duration and sNfL level (ß = 0.65, p = 0.0280). After adjusted for covariates, this relationship still (ß = 0.82, p = 0.0052). Segmented regression showed that the turning point of sleep duration was 7 h 1 h decrease in sleep duration was significantly associated with -1.26 higher sNfL level (95 % CI: 2.25, -0.28; p = 0.0115) when sleep duration <7 h; however, 1 h increase in sleep duration was significantly associated with 3.20 higher sNfL level (95 % CI: 2.13, 4.27; p < 0.0001) when sleep duration >7 h. Furthermore, the stratified analysis indicated that the associations between sleep duration and sNfL level were stronger among those normal body mass index and trouble sleeping (p-interaction <0.0001 and 0.0003). Conclusion: In summary, there was a J-shaped relationship between sleep duration and sNfL level in the United States of America representative group, these may suggest that extreme sleep duration can be deleterious judged by sNfL level. And still need large cohort study to determine the accurate relationship, and cluster analysis to infer the nervous disease connected with extreme sleep duration.

Causal Associations of DNA Methylation and Cardiovascular Disease: A Two-Sample Mendelian Randomization Study.

Background: There is growing evidence that concentrations of DNA methylation are associated with cardiovascular disease; however, it is unclear whether this association reflects a causal relationship. Methods: We utilized a two-sample Mendelian randomization (MR) approach to investigate whether DNA methylation can affect the risk of developing cardiovascular disease in human life. We primarily performed the inverse variance weighted (IVW) method to analyze the causal effect of DNA methylation on multiple cardiovascular diseases. Additionally, to ensure the robustness of our findings, we conducted several sensitivity analyses using alternative methodologies. These analysis methods included maximum likelihood, MR-Egger regression, weighted median method, and weighted model methods. Results: Inverse variance weighted estimates suggested that an SD increase in DNA methylation Hannum age acceleration exposure increased the risk of cardiac arrhythmias (OR = 1.03, 95% CI 1.00-1.05, p = 0.0290) and atrial fibrillation (OR = 1.03, 95% CI 1.00-1.05, p = 0.0022). We also found that an SD increase in DNA methylation PhenoAge acceleration exposure increased the risk of heart failure (OR = 1.01, 95% CI 1.00-1.03, p = 0.0362). Exposure to DNA methylation-estimated granulocyte proportions was found to increase the risk of hypertension (OR = 1.00, 95% CI 1.00-1.0001, p = 0.0291). Exposure to DNA methylation-estimated plasminogen activator inhibitor-1 levels was found to increase the risk of heart failure (OR = 1.00, 95% CI 1.00-1.00, p = 0.0215). Conclusion: This study reveals a causal relationship between DNA methylation and CVD. Exposed to high levels of DNA methylation Hannum age acceleration inhabitants with an increased risk of cardiac arrhythmias and atrial fibrillation. DNA methylation PhenoAge acceleration levels exposure levels were positively associated with the increased risk of developing heart failure. This has important implications for the prevention of cardiovascular diseases.

Effect of holographic Guasha on sleep quality of older adults with hypertension in the community: A prospective study.

To explore the effect of holographic Guasha therapy on the Pittsburg Sleep Quality Index (PSQI) and Hamilton Anxiety Rating Scale (HAMA) in older adults with hypertension living in the community. This prospective study was conducted from July 2019 to December 2020. Older adults with hypertension (systolic pressure ≥ 140 mm Hg, diastolic pressure ≥ 90 mm Hg) were divided into the control and Guasha groups. The PSQI and HAMA were assessed before and after 4 weeks of intervention. 62 patients were enrolled, with 31/group (Guasha: 72.4 ±â€…6.9 years, 23.0 ±â€…3.1 kg/m2; control: 71.4 ±â€…6.3 years; 22.9 ±â€…2.9 kg/m2). The total PSQI score did not decrease in the control group after 4 weeks (from 14.8 ±â€…1.2 to 14.8 ±â€…1.8, P = .498) but decreased in the Guasha group (from 14.9 ±â€…1.1 to 6.8 ±â€…3.5, P < .001). All PSQI subscores decreased in the Guasha group after 4 weeks of Guasha intervention (all P < .05), except for the use of sleep medication, since the use of such drugs was an exclusion criterion. The HAMA index scores did not change in the control or Guasha group (both P > .05). Holographic Guasha appears to achieve better sleep outcomes than conventional treatment in improving the sleep quality of older adults with hypertension living in the community. The participants were not randomly assigned to the treatments, and the results should be confirmed in a formal trial.

Solid-State Red Carbon Dots Based on Biomass Furan Derivatives.

In the preparation of carbon dots (CDs), precursors are crucial, and abundant precursors endow CDs with various structures and fluorescence characteristics. Furan (FU) and its derivatives are considered excellent carbonization materials due to their π conjugated structures and active functional groups, such as hydroxyl and aldehyde groups. Herein, we prepare FU-derivative-based CDs by a solvothermal method and investigate the influences of the precursor structure on the fluorescence characteristics. Surprisingly, CDs prepared from 5-hydroxymethylfurfural (HMF) with both aldehyde and hydroxyl groups exhibit red-shifted fluorescence characteristics in the solid state. We postulate that this solid-state fluorescence characteristic is due to the enhancement of supramolecular cross-linking fluorescence between CDs. The unique precursor structure leads to carboxyl groups on the surface of HMF-CDs that are conducive to the hydrogen bond formation. As the concentration of CDs increases, the hydrogen bonding effect increases, leading to a red-shift in the fluorescence wavelength. Therefore, basically full-color CDs/poly(vinyl alcohol) (PVA) phosphor-based light-emitting diodes can be achieved by controlling the degree of supramolecular cross-linking of CDs in PVA. This research provides a new approach for the preparation of solid-state luminescent CDs.

Predicting cardiovascular risk stratification in apparently healthy population by using noninvasive ultrafast ultrasound imaging.

BACKGROUND: To investigate the association between cardiovascular risk estimated using the Framingham Risk Score (FRS) and carotid stiffening determined using ultrafast pulse wave velocity (ufPWV) measurements in apparently healthy individuals. METHODS: We enrolled 1034 apparently healthy participants without known cardiovascular disease who underwent ufPWV measurements. Clinical and laboratory findings, carotid intima-media thickness (cIMT), pulse wave velocity at the beginning of systole (PWV-BS), and pulse wave velocity at the end of systole (PWV-ES) were assessed. In FRS assessments based on major cardiovascular risk factors (CVRFs), participants were assigned into three risk categories: low risk (<10%, n = 679), intermediate risk (10-20%, n = 191), and high risk (>20%, n = 164); the low-risk category was further subdivided into three subcategories: < 1% (n = 58), 1%- 5% (n = 374) and > 5% (n = 247). Multivariate logistic regression analyses with crude and adjusted odds ratios (ORs) were used to evaluate the association of carotid stiffening and FRS-based risk stratification. RESULTS: Carotid stiffening indicated by PWV-BS and PWV-ES differed notably between the FRS-estimated low-risk vs. intermediate-risk and high-risk categories, but only PWV-ES differed notably among the low-risk subcategories (all p < 0.010), and correlated notably with the FRS-estimated risk most obviously in low-risk participants (r = 0.517). In participants with cIMT < 0.050 cm, only PWV-ES differed significantly among the FRS-estimated risk categories (all p < 0.001). Increased PWV-BS (adjusted OR: 1.49; p = 0.003) and PWV-ES (adjusted OR: 1.29; p = 0.007) were both associated with FRS categories independent of conventional CVRFs in low- vs. intermediate-risk categories, but not in low- vs. high-risk categories (all p > 0.050). CONCLUSION: In vivo imaging of carotid stiffening by ufPWV measurements is independently linked to FRS categories, and ufPWV indices may help stratify differing levels of cardiovascular risk in apparently healthy young people. AVAILABILITY OF DATA AND MATERIAL: Data generated or analyzed during the study are available from the corresponding author by reasonable request.

Lithium Borate Polycarbonates for High-Capacity Solid-State Composite Cathodes.

Improving composite cathode function is key to the success of the solid-state battery. Maximizing attainable cathode capacity and retention requires integrating suitable polymeric binders that retain a sufficiently high ionic conductivity and long-term chemo-mechanical stability of the cathode active material-solid-electrolyte-carbon mixture. Herein, we report block copolymer networks composed of lithium borate polycarbonates and poly(ethylene oxide) that improved the capacity (200 mA h g-1 at 1.75 mA cm-2) and capacity retention (94% over 300 cycles) of all-solid-state composite cathodes with nickel-rich LiNi0.8Co0.1Mn0.1O2 cathode active material, Li6PS5Cl solid electrolyte, and carbon. Tetrahedral B(OR)2(OH)2- anions immobilized on the polycarbonate segments provide hydrogen-bonding chain crosslinking and selective Li-counterion conductivity, parameterized by Li-ion transference numbers close to unity (tLi+ ~ 0.94). With 90 wt% polycarbonate content and a flexible low glass transition temperature backbone, the single-ion conductors achieved high Li-ion conductivities of 0.2 mS cm-1 at 30°C. The work should inform future binder design for improving the processability of cathode composites towards commercialising solid-state batteries, and allow use in other cell configurations, such as lithium-sulphur cathode designs.

Defective ferritinophagy and imbalanced iron metabolism in PBDE-47-triggered neuronal ferroptosis and salvage by Canolol.

The brominated flame retardant 2,2',4,4'-tetrabromodiphenyl ether (PBDE-47) is a ubiquitous environmental pollutant that causes neurotoxicity. However, incomplete understanding of the underlying mechanisms has hampered the development of effective intervention strategies. Oxidative stress and related cell death are the modes of action for PBDE-47 neurotoxicity, which are also the characteristics of ferroptosis. Nonetheless, the role of ferroptosis in PBDE-47-induced neurotoxicity remains unclear. In the present study, we found that PBDE-47 triggered ferroptosis in neuron-like PC12 cells, as evidenced by intracellular iron overload, lipid peroxidation, and mitochondrial damage. This was confirmed by ferroptosis inhibitors including the lipid reactive oxygen species scavenger ferrostatin-1 and iron chelator deferoxamine mesylate. Mechanistically, PBDE-47 impaired ferritinophagy by disrupting nuclear receptor coactivator 4-mediated lysosomal degradation of the iron storage protein ferritin. Moreover, PBDE-47 disturbed iron metabolism by increasing cellular iron import via upregulation of transferrin receptor 1 and decreasing cellular iron export via downregulation of ferroportin 1 (FPN1). Intriguingly, rescuing lysosomal function by overexpressing cathepsin B (CatB) mitigated PBDE-47-induced ferroptosis by partially restoring dysfunctional ferritinophagy and enhancing iron excretion via the upregulation of FPN1. However, FPN1 knockdown reversed the beneficial effects of CatB overexpression on the PBDE-47-induced iron overload. Finally, network pharmacology integrated with experimental validation revealed that Canolol, the main phenolic compound in canola oil, protected against PBDE-47-evoked iron overload, resulting in ferroptosis by restoring defective ferritinophagy and improving abnormal iron metabolism via lowering iron uptake and facilitating iron excretion. Overall, these data suggest that ferroptosis is a novel mechanism of PBDE-47-induced neuronal death and that manipulation of ferritinophagy and iron metabolism via Canolol represents a promising therapeutic strategy.

Coordinated d-p hybridized hcp@fcc NiRu alloy doped by interstitial atoms for boosting urea-assisted simulated seawater electrolysis at industrial current densities.

The production of hydrogen through seawater electrolysis has recently garnered increasing concern. However, hydrogen evolution reaction (HER) by alkaline seawater electrocatalysis is severely impeded by the slow H2O adsorption and H* binding kinetics at industrial current densities. Herein, a face-centered cubic/hexagonal close packed (fcc/hcp) NiRu alloy heterojunction was fabricated on Ni foam (N doped NiRu-inf/NF) by a low-temperature nitrogen plasma activation. Simultaneously, nitrogen atoms are introduced into the alloy to facilitate d-p hybridization. When N doped NiRu-inf/NF is integrated into a dual-electrode cell for urea-assisted seawater electrolysis, it achieves 100 mA cm-2 with an ultra-low voltage of 1.36 V and excellent stability. Density functional theory (DFT) verifies that the robust d-p hybridization among Ni, Ru and N exhibits more energy level matching for H2O molecule adsorption at the Ru sites, while simultaneously reducing the interaction between H* and Ni sites in N-doped NiRu-inf.

3D Directional Assembly of Liquid Crystal Molecules.

The precise construction of hierarchically long-range ordered structures using molecules as fundamental building blocks can fully harness their anisotropy and potential. However, the 3D, high-precision, and single-step directional assembly of molecules is a long-pending challenge. Here, a 3D directional molecular assembly strategy via femtosecond laser direct writing (FsLDW) is proposed and the feasibility of this approach using liquid crystal (LC) molecules as an illustrative example is demonstrated. The physical mechanism for femtosecond (fs) laser-induced assembly of LC molecules is investigated, and precise 3D arbitrary assembly of LC molecules is achieved by defining the discretized laser scanning pathway. Additionally, an LC-based Fresnel zone plate array with polarization selection and colorization imaging functions is fabricated to further illustrate the potential of this method. This study not only introduces a 3D high-resolution alignment method for LC-based functional devices but also establishes a universal protocol for the precise 3D directional assembly of anisotropic molecules.

Bestatin attenuates breast cancer stemness by targeting puromycin-sensitive aminopeptidase.

Breast cancer is a prevalent malignant tumor among women with an increasing incidence rate annually. Breast cancer stem cells (BCSCs) are integral in impeding tumor advancement and addressing drug resistance. Bestatin serves as an adjuvant chemotherapy, triggering apoptosis in cancer cells. In this study, the effects of bestatin on sorted BCSCs from breast cancer cell lines have been studied. Our results indicated that bestatin inhibits the migration and proliferation of breast cancer cells by reducing the stemness of BCSCs both in vitro and in vivo. Puromycin-sensitive aminopeptidase is implicated in the process through the regulation of cell cycle, resulting in heightened cell apoptosis and diminished cell proliferation of BCSCs. Our study suggest that targeting cancer stem cell may offer a promising approach in breast cancer treatment, presenting noval therapeutic strategies for patients with breast cancer.

Assessing the Utility of a Genotype-Guided Tacrolimus Equation in African American Kidney Transplant Recipients: A Single Institution Retrospective Study.

Tacrolimus metabolism is heavily influenced by the CYP3A5 genotype, which varies widely among African Americans (AA). We aimed to assess the performance of a published genotype-informed tacrolimus dosing model in an independent set of adult AA kidney transplant (KTx) recipients. CYP3A5 genotypes were obtained for all AA KTx recipients (n = 232) from 2010 to 2019 who met inclusion criteria at a single transplant center in Philadelphia, Pennsylvania, USA. Medical record data were used to calculate predicted tacrolimus clearance using the published AA KTx dosing equation and two modified iterations. Observed and model-predicted trough levels were compared at 3 days, 3 months, and 6 months post-transplant. The mean prediction error at day 3 post-transplant was 3.05 ng/mL, indicating that the model tended to overpredict the tacrolimus trough. This bias improved over time to 1.36 and 0.78 ng/mL at 3 and 6 months post-transplant, respectively. Mean absolute prediction error-a marker of model precision-improved with time to 2.33 ng/mL at 6 months. Limiting genotype data in the model decreased bias and improved precision. The bias and precision of the published model improved over time and were comparable to studies in previous cohorts. The overprediction observed by the published model may represent overfitting to the initial cohort, possibly limiting generalizability.

Investigating the effects of rare ginsenosides on hyperuricemia and associated sperm damage via nontargeted metabolomics and gut microbiota.

ETHNOPHARMACOLOGICAL RELEVANCE: In ancient times, ginseng was used for hyperuricemia treatment as described in the classic traditional Chinese medical text Shang Han Lun. Recent studies have shown that common ginsenosides and rare ginsenosides (RGS) are the main active compounds in ginseng. RGS have higher activity and are less studied in the treatment of hyperuricemia. AIM OF THE STUDY: To determine whether RGS prevents and ameliorates potassium oxonate(PO)-induced hyperuricemia and concomitant spermatozoa damage in mice and the possible underlying mechanisms. MATERIALS AND METHODS: Potassium oxonate (PO, 300 mg/kg) induced hyperuricemia in mice via the oral administration of RGS (50, 100, or 200 mg/kg) or allopurinol (ALL, 5 mg/kg) for 35 days. Uric acid (UA) and xanthine oxidase (XO) levels were measured to assess the degree of histopathological damage in the liver, kidney, and testis, and renal creatinine (CRE), urea nitrogen (BUN), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and inflammatory factor (IL-1ß) levels were measured to calculate the sperm density. Mechanisms were also explored based on blood and urine metabolomics and the gut microbiota. RESULTS: In this study, we demonstrated that RGS containing Rg3, Rk1, Rg6, and Rg5 could reduce serum UA levels, inhibit serum and hepatic XO activity, reduce renal CRE and BUN levels, further restore renal SOD and GSH activities, reduce the accumulation of MDA in the kidneys, and attenuate the production of renal IL-1ß. RGS was able to restore sperm density. Metabolomic analysis revealed that RGS improved sphingolipid metabolism, pyrimidine metabolism, and other metabolic pathways. 16S rDNA sequencing revealed that RGS could increase gut microbial diversity, restore the Firmicutes/Bacteroidetes (F/B) ratio, and adjust the intestinal microbial balance. Spearman's correlation analysis revealed a correlation between differentially metabolites and the gut microbiota. Lactobacillus and Akkermansia are the core genera. CONCLUSION: RGS can be a candidate for the prevention and amelioration of hyperuricemia and concomitant sperm damage. Its mechanism of action is closely related to sphingolipid metabolism, pyrimidine metabolism, and the modulation of gut microbiota, such as Lactobacillus and Akkermansia.