Research on PIVAS risk assessment and control strategy based on quality risk management (QRM).

OBJECTIVE: This study aims to evaluate the effectiveness of the Quality Risk Management (QRM) system in hospital pharmacy intravenous admixture services (PIVAS). METHODS: Failure Modes and Effects Analysis (FMEA) and risk matrix methods were used to systematically assess the critical risk points in PIVAS. By collecting and comparing relevant data from 2019 to 2023, key performance indicators (KPIs) before and after the implementation of the QRM system were quantitatively evaluated. RESULTS: The results showed that the safety and efficiency of pharmacy services significantly improved after the implementation of the QRM system. The medication error rate significantly decreased from 3.2% to 1.1%, the average medication preparation time reduced from 15.5 min to 8.2 min, and staff satisfaction increased from 6.0 to 8.5 points. Other indicators, such as cross-contamination rates and handling errors, also showed significant improvement (all outcomes p < 0.001). DISCUSSION: Systematic risk management effectively enhanced the operational performance of PIVAS, reduced medication errors, and improved the quality of healthcare services. This study highlights the key role of QRM in enhancing medication safety and productivity, providing empirical support for the implementation of similar systems in other healthcare institutions.

An updated AL-Base reveals ranked enrichment of immunoglobulin light chain variable genes in AL amyloidosis.

Background: Each monoclonal antibody light chain associated with AL amyloidosis has a unique sequence. Defining how these sequences lead to amyloid deposition could facilitate faster diagnosis and lead to new treatments. Methods: Light chain sequences are collected in the Boston University AL-Base repository. Monoclonal sequences from AL amyloidosis, multiple myeloma and the healthy polyclonal immune repertoire were compared to identify differences in precursor gene use, mutation frequency and physicochemical properties. Results: AL-Base now contains 2,193 monoclonal light chain sequences from plasma cell dyscrasias. Sixteen germline precursor genes were enriched in AL amyloidosis, relative to multiple myeloma and the polyclonal repertoire. Two genes, IGKV1-16 and IGLV1-36 , were infrequently observed but highly enriched in AL amyloidosis. The number of mutations varied widely between light chains. AL-associated κ light chains harbored significantly more mutations compared to multiple myeloma and polyclonal sequences, whereas AL-associated λ light chains had fewer mutations. Machine learning tools designed to predict amyloid propensity were less accurate for new sequences than their original training data. Conclusions: Rarely-observed light chain variable genes may carry a high risk of AL amyloidosis. New approaches are needed to define sequence-associated risk factors for AL amyloidosis. AL-Base is a foundational resource for such studies.

Melatonin Ameliorates Abnormal Sleep-Wake Behavior via Facilitating Lipid Metabolism in a Zebrafish Model of Parkinson's Disease.

Sleep-wake disorder is one of the most common nonmotor symptoms of Parkinson's disease (PD). Melatonin has the potential to improve sleep-wake disorder, but its mechanism of action is still unclear. Our data showed that melatonin only improved the motor and sleep-wake behavior of a zebrafish PD model when melatonin receptor 1 was present. Thus, we explored the underlying mechanisms by applying a rotenone model. After the PD zebrafish model was induced by 10 nmol/L rotenone, the motor and sleep-wake behavior were assessed. In situ hybridization and real-time quantitative PCR were used to detect the expression of melatonin receptors and lipid-metabolism-related genes. In the PD model, we found abnormal lipid metabolism, which was reversed by melatonin. This may be one of the main pathways for improving PD sleep-wake disorder.

Elevations of N-Terminal Mid-Fragment of Osteocalcin and Cystatin C Levels are Associated with Disorders of Glycolipid Metabolism and Abnormal Bone Metabolism in Patients with Type 2 Diabetes Mellitus Complicated with Osteoporosis.

ABSTRACT: Type 2 diabetes mellitus (T2DM) patients always develop osteoporosis (OP). We examined correlations of N-terminal mid-fragment of osteocalcin (N-MID) and cystatin C (Cys C) levels with glycolipid metabolism, bone metabolism markers, and bone mineral density (BMD) in elderly T2DM-OP patients. Grouping was performed as per whether T2DM patients developed OP (OP group) or not (N-OP group). N-MID and Cys C were measured using enzyme-linked immunosorbent assay, with correlations with glycolipid metabolism, bone metabolism indicators, and BMD analyzed using Pearson's correlation coefficient. Elderly T2DM-OP patients showed elevated disease duration, age, body mass index, glycated hemoglobin (HbA1c), Homer's insulin resistance (HOMA-IR), total cholesterol (TC), beta-carboxy-terminal crosslinked telopeptide of type 1 collagen (ß-CTX), tartrate-resistant acid phosphatase 5b (TRACP-5b), N-MID and Cys C levels, and reduced high-density lipoprotein cholesterol (HDL-C), bone alkaline phosphatase (B-ALP), aminoterminal propeptide of type I procollagen (PINP), carboxyterminal propeptide of type I procollagen (PICP), BMD, and calcium supplementation. N-MID and Cys C were positively correlated with HbA1c, HOMA-IR, TC, ß-CTX, and TRACP-5b and negatively with HDL-C, B-ALP, PINP, PICP, and BMD in elderly T2DM-OP patients. Conclusively, the abnormal elevations of serum N-MID and Cys C were associated with glycolipid metabolism disorder, abnormal bone metabolism, and decreased BMD in elderly T2DM-OP patients.

Cascade Cyclization of N-Cyanamide Alkenes for the Divergent Synthesis of Azido-, Nitro-, and Alkenyl-Containing Pyrroloquinazolinones.

Radical cascade cyclizations of N-cyanamide alkenes have been developed for the divergent synthesis of pyrroloquinazolinones bearing azido, alkenyl, and nitro groups by controlling the reaction conditions. The reaction temperature and the loading of the base play important roles in the different reaction pathways. These reactions are characterized by wide functional group compatibility and mild conditions.

Functional group-specific reduction of Cr(VI) by low molecular weight organic acids in frozen solution: Kinetics, mechanism and DFT calculation.

Low molecular weight organic acids (LMWOA) are commonly present in natural water and play a pivotal role in the reduction of Cr(VI). In frozen solutions, the efficiency of Cr(VI) reduction is significantly enhanced due to the freezing concentration effect. However, this facilitation is found to be contingent upon the functional groups of LMWOA in this study. To be specific, LMWOA and Cr(VI) can form five-membered ring complexes, which greatly enhance electron transfer efficiency through Ligand-to-Metal Charge Transfer (LMCT). DFT calculations indicate that oxygen-containing groups located on carbon atoms at α positions play a crucial role in forming these complexes, ultimately determining the kinetics of Cr(VI) reduction. Moreover, freezing not only increases proton concentrations but also reduces free water molecule content in the liquid-like layer (LLL), thereby affecting LMWOA species through regulation of protonation and hydrolysis, and subsequently impacting reaction mechanisms. The stoichiometric ratios between LMWOA and Cr(VI) exceed theoretical values due to complexation with Cr(III). The reduction of Cr(VI) by LMWOA in frozen solutions is inhibited by soil solution, while the degree of inhibition varies among different types of LMWOA.

Polyfunctional Arylamine Based Nanofiltration Membranes with Enhanced Aggressive Organic Solvents Resistance.

Organic solvent nanofiltration (OSN) membranes with high separation performance and excellent stability in aggressive organic solvents are urgently desired for chemical separation. Herein, we utilized a polyfunctional arylamine tetra-(4-aminophenyl) ethylene (TAPE) to prepare a highly cross-linked polyamide membrane with a low molecular weight cut-off (MWCO) of 312 Da. Owing to its propeller-like conformation, TAPE formed micropores within the polyamide membrane and provided fast solvent transport channels. Importantly, the rigid conjugated skeleton and high connectivity between micropores effectively prevented the expansion of the polyamide matrix in aggressive organic solvents. The membrane maintained high separation performance even immersed in N,N-dimethylformamide for 90 days. Based on the aggregation-induced emission (AIE) effect of TAPE, the formation of polyamide membrane can be visually monitored by fluorescence imaging technology, which achieved visual guidance for membrane fabrication. This work provides a vital foundation for utilizing polyfunctional monomers in the interfacial polymerization reaction to prepare high-performance OSN membranes.

Clinicopathological association of CD93 expression in gastric adenocarcinoma.

AIMS: CD93 was recently identified as a promising therapeutic target for angiogenesis blockade in various tumors. Herein, we aimed to investigate the expression and clinicopathological significance of CD93 in gastric adenocarcinoma. METHODS: The gene expression of CD93 gastric adenocarcinoma was assessed using The Cancer Genome Atlas (TCGA) dataset. We then analyzed CD93 expression in 404 cases of gastric adenocarcinoma using immunohistochemistry. Clinicopathological associations and prognostic implications of CD93 expression were further investigated. RESULTS: Using the TCGA dataset, we observed a significantly elevated CD93 gene expression in gastric adenocarcinoma compared to normal gastric tissues. The immunohistochemistry assay revealed a highly variable CD93 expression among patients with gastric adenocarcinoma, consistently demonstrating higher intratumor expression than in adjacent normal tissues. Notably, CD93 was predominantly expressed on the membrane of CD31+ vascular endothelial cells. Furthermore, patients with higher CD93 expression demonstrated significantly poorer overall survival. Accordingly, higher CD93 expression was associated with deeper invasion and a higher possibility of lymph node metastasis and developing tumor thrombus. Cox proportional hazards regression suggested CD93 expression was an independent predictor for the prognosis of patients with gastric adenocarcinoma. CONCLUSIONS: Our study revealed a significantly higher CD93 expression in gastric adenocarcinoma when compared with adjacent normal gastric tissues, and demonstrated its predominant expression on vascular endothelial cells. Our findings also highlighted the clinicopathological significance of CD93 in gastric adenocarcinoma, shedding light on a potential therapeutic target.

GBA-AAV mitigates sleep disruptions and motor deficits in mice with REM sleep behavior disorder.

Sleep disturbances, including rapid eye movement sleep behavior disorder (RBD), excessive daytime sleepiness, and insomnia, are common non-motor manifestations of Parkinson's disease (PD). Little is known about the underlying mechanisms, partly due to the inability of current rodent models to adequately mimic the human PD sleep phenotype. Clinically, increasing studies have reported that variants of the glucocerebrosidase gene (GBA) increase the risk of PD. Here, we developed a mouse model characterized by sleep-wakefulness by injecting α-synuclein preformed fibronectin (PFF) into the sublaterodorsal tegmental nucleus (SLD) of GBA L444P mutant mice and investigated the role of the GBA L444P variant in the transition from rapid eye movement sleep behavior disorder to PD. Initially, we analyzed spectral correlates of REM and NREM sleep in GBA L444P mutant mice. Importantly, EEG power spectral analysis revealed that GBA L444P mutation mice exhibited reduced delta power during non-rapid eye movement (NREM) sleep and increased theta power (8.2-10 Hz) in active rapid eye movement (REM) sleep phases. Our study revealed that GBA L444P-mutant mice, after receiving PFF injections, exhibited increased sleep fragmentation, significant motor and cognitive dysfunctions, and loss of dopaminergic neurons in the substantia nigra. Furthermore, the over-expression of GBA-AAV partially improved these sleep disturbances and motor and cognitive impairments. In conclusion, we present the initial evidence that the GBA L444P mutant mouse serves as an essential tool in understanding the complex sleep disturbances associated with PD. This model further provides insights into potential therapeutic approaches, particularly concerning α-synuclein accumulation and its subsequent pathological consequences.

Advances in Laser Powder Bed Fusion of Tungsten, Tungsten Alloys, and Tungsten-Based Composites.

In high-tech areas such as nuclear fusion, aerospace, and high-performance tools, tungsten and its alloys are indispensable due to their high melting point, low thermal expansion, and excellent mechanical properties. The rise of Additive Manufacturing (AM) technologies, particularly Laser Powder Bed Fusion (L-PBF), has enabled the precise and rapid production of complex tungsten parts. However, cracking and densification remain major challenges in printing tungsten samples, and considerable efforts have been made to study how various processing conditions (such as laser power, scanning strategy, hatch spacing, scan speed, and substrate preheating) affect print quality. In this review, we comprehensively discuss various critical processing parameters and the impact of oxygen content on the control of the additive manufacturing process and the quality of the final parts. Additionally, we introduce additive manufacturing-compatible W materials (pure W, W alloys, and W-based composites), summarize the differences in their mechanical properties, densification, and microstructure, and further provide a clear outlook for developing additive manufactured W materials.

Switchable Vanadium Dioxide Metasurface for Terahertz Ultra-Broadband Absorption and Reflective Polarization Conversion.

Based on the unique insulator-metal phase transition property of vanadium dioxide (VO2), we propose an integrated metasurface with a switchable mechanism between ultra-broadband absorption and polarization conversion, operating in the terahertz (THz) frequency range. The designed metasurface device is constructed using a stacked structure composed of VO2 quadruple rings, a dielectric layer, copper stripes, VO2 film, a dielectric layer, and a copper reflection layer. Our numerical simulations demonstrate that our proposed design, at high temperatures (above 358 K), exhibits an ultra-broadband absorption ranging from 4.95 to 18.39 THz, maintaining an absorptivity greater than 90%, and achieves a relative absorption bandwidth of up to 115%, significantly exceeding previous research records. At room temperature (298 K), leveraging VO2's insulating state, our proposed structure transitions into an effective polarization converter, without any alteration to its geometry. It enables efficient conversion between orthogonal linear polarizations across 3.51 to 10.26 THz, with cross-polarized reflection exceeding 90% and a polarization conversion ratio over 97%. More importantly, its relative bandwidth reaches up to 98%. These features highlight its wide-angle, extensive bandwidth, and high-efficiency advantages for both switching functionalities. Such an ultra-broadband convertible design offers potential applications in optical switching, temperature dependent optical sensors, and other tunable THz devices in various fields.

A high-performance magnesium/lithium hybrid-ion battery using a hollow multi-layered NiS/Co3S4/carbon cathode and an all-phenyl-complex-based electrolyte.

Magnesium-lithium hybrid batteries (MLHBs) using a dual-ion electrolyte and safe Mg anode have promising potential for high-performance energy storage. Here, we develop an MLHB constructed of a hollow multi-layered NiS/Co3S4/carbon cathode and an all-phenyl-complex/lithium chloride (APC-LiCl) electrolyte. The hollow multi-layered structure and carbon matrix accommodate volumetric expansion and facilitate electrolyte penetration. The APC-LiCl electrolyte displays a stable electrochemical window. The MLHB shows a high specific capacity of 398 mA h g-1 after 100 cycles at 0.2 A g-1, and a stable capacity at 1.0 A g-1 after cycling 500 times. Moreover, stable rate performance and temperature tolerance are achievable. These findings would enable this design to be promising for developing other hybrid battery systems.

Changes in slow-wave sleep characteristics in Parkinson's disease patients with mild-moderate depression.

INTRODUCTION: Depression and sleep disturbances are commonly seen non-motor symptoms in patients with Parkinson's disease (PD). This study used polysomnography to examine the relationship between mild-moderate depression in PD and sleep characteristics, particularly slow wave activities (SWA). METHODS: 59 PD patients were split into two groups: nd-PD (n = 27) (patients with PD without depression) and d-PD (n = 32) (patients with PD with mild-moderate depression). Their clinical features, polysomnography parameters, and demographics were evaluated. Early and late sleep SWA spectrum densities and overnight SWA decline in different brain regions were particularly analyzed. RESULTS: Non-rapid eye movement 3 (N3) sleep duration and percentage were greater in the d-PD group. N3 percentage was linked to depression (p = 0.014). During late sleep, higher SWA (0.5-4Hz) in the frontal and central regions, higher low-SWA (0.5-2Hz) in the whole brain, central and occipital regions, and higher high-SWA (2-4Hz) in the frontal region was observed in the d-PD group. During early sleep, there was also higher low-SWA (0.5-2Hz) in the occipital region. Patients in d-PD group exhibited reduced overnight high-SWA (2-4Hz) decline (Δhigh-SWA) in the whole brain and occipital regions. Δhigh-SWA(2-4Hz) in the occipital region were associated with depression (p = 0.049). CONCLUSION: PD patients with mild-moderate depression have impaired slow wave sleep, exhibiting as increased N3 sleep, SWA, and reduced overnight SWA decline. This implies that synaptic strength reduction during sleep and impaired synaptic homeostasis regulation may be associated with depression in PD. Reduced overnight high-SWA decline in the occipital region may serve as a novel electrophysiological biomarker for indicating depression in PD.

Acteoside alleviates lipid peroxidation by enhancing Nrf2-mediated mitophagy to inhibit ferroptosis for neuroprotection in Parkinson's disease.

Increasing evidence underscores the pivotal role of ferroptosis in Parkinson's Disease (PD) pathogenesis. Acteoside (ACT) has been reported to possess neuroprotective properties. However, the effects of ACT on ferroptosis and its molecular mechanisms remain unknown. This study aimed to explore whether ACT can regulate ferroptosis in dopaminergic (DA) neurons within both in vitro and in vivo PD models and to elucidate the underlying regulatory mechanisms. PD models were established and treated with various concentrations of ACT. Cell viability assays, Western blot, lipid peroxidation assessments, immunohistochemistry, and transmission electron microscopy were employed to confirm ACT's inhibition of ferroptosis and its protective effect on DA neurons across PD models. Immunofluorescence staining, MitoSOX staining, and confocal laser scanning microscopy further validated ACT's regulation regulatory effects on ferroptosis via the Nrf2-mitophagy pathway. Four animal behavioral tests were used to assess behavioral improvements in PD animals. ACT inhibited ferroptosis in PD models in vitro, as evidenced by increased cell viability, the upregulation of GPX4 and SLC7A11, reduced lipid peroxides, and attenuation of mitochondrial morphological alterations typical of ferroptosis. By activating the Nrf2-mitophagy axis, ACT enhanced mitochondrial integrity and reduced lipid peroxidation, mitigating ferroptosis. These in vitro results were consistent with in vivo findings, where ACT treatment significantly preserved DA neurons, curbed ferroptosis in these cells, and alleviated cognitive and behavioral deficits. This study is the first demonstration of ACT's capability to inhibit neuronal ferroptosis and protect DA neurons, thus alleviating behavioral and cognitive impairments in both in vitro and in vivo PD models. Furthermore, The suppression of ferroptosis by ACT is achieved through the activation of the Nrf2-mitophagy signaling pathway. Our results show that ACT is beneficial for both treating and preventing PD. They also offer novel therapeutic options for treating PD and molecular targets for regulating ferroptosis.

W-Shaped π-Extended Double Undecabenzo[7]helicene.

A chiral W-shaped fully π-extended double [7]helicene (ED7H) has been synthesized and fully characterized. It displays fluorescence emission (λem = 636 nm) with a quantum yield (Φf) of 0.10. In comparison to its X-shaped and monomict π-extended [7]helicene analogues, enantiopure W-shaped ED7H exhibited superior chiral optical characteristics, including distinct circular dichroism signals from 400 to 650 nm, a good dissymmetric emission factor |glum| of 4 × 10-3, and a circularly polarized luminescence brightness value BCPL of 42 M-1 cm-1.

Social life of free-living amoebae in aquatic environment- comprehensive insights into interactions of free-living amoebae with neighboring microorganisms.

Free-living amoebae (FLA) are prevalent in nature and man-made environments, and they can survive in harsh conditions by forming cysts. Studies have discovered that some FLA species are able to show pathogenicity to human health, leading to severe infections of central nervous systems, eyes, etc. with an extremely low rate of recovery. Therefore, it is imperative to establish a surveillance framework for FLA in environmental habitats. While many studies investigated the risks of independent FLA, interactions between FLA and surrounding microorganisms determined microbial communities in ecosystems and further largely influenced public health. Here we systematically discussed the interactions between FLA and different types of microorganisms and corresponding influences on behaviors and health risks of FLA in the environment. Specifically, bacteria, viruses, and eukaryotes can interact with FLA and cause either enhanced or inhibited effects on FLA infectivity, along with microorganism community changes. Therefore, considering the co-existence of FLA and other microorganisms in the environment is of great importance for reducing environmental health risks.

The Effects of Pore Defects in π-Extended Pentadecabenzo[9]helicene.

The introduction of precise pore defects into nanocarbon structures results in the emergence of distinct physicochemical characteristics. However, there is a lack of research on non-planar chiral nanographene involving precise pore defects. Herein, we have developed two analogues to the π-extended pentadecabenzo[9]helicene (EP9H) containing embedded pore defects. Each molecule, namely extended dodecabenzo[7]helicene (ED7H; 1) or extended nonabenzo[5]helicene (EN5H; 2), exhibits dual-state emission. Significantly, the value of |glum| of 1 is exceptionally high at 1.41 × 10-2 in solution and BCPL as 254 M-1 cm-1. In PMMA film, |glum| of 1 is 8.56 × 10-3, and in powder film, it is 5.00 × 10-3. This study demonstrates that nanocarbon molecules with pore defects exhibit dual-state emission properties while maintaining quite good chiral luminescence properties. It was distinguished from the aggregation-caused quenching (ACQ) effect corresponding to the nanocarbon without embedded defect. Incorporating pore defects into chiral nanocarbon molecules also simplifies the synthesis process and enhances the solubility of the resulting product. These findings suggest that the introduction of pore defects can be a viable approach to improve nanocarbon molecules.

Nano-sized polystyrene and magnetite collectively promote biofilm stability and resistance due to enhanced oxidative stress response.

Despite the growing prevalence of nanoplastics in drinking water distribution systems, the collective influence of nanoplastics and background nanoparticles on biofilm formation and microbial risks remains largely unexplored. Here, we demonstrate that nano-sized polystyrene modified with carboxyl groups (nPS) and background magnetite (nFe3O4) nanoparticles at environmentally relevant concentrations can collectively stimulate biofilm formation and prompt antibiotic resistance. Combined exposure of nPS and nFe3O4 by P. aeruginosa biofilm cells stimulated intracellular reactive oxidative species (ROS) production more significantly compared with individual exposure. The resultant upregulation of quorum sensing (QS) and c-di-GMP signaling pathways enhanced the biosynthesis of polysaccharides by 50 %- 66 % and increased biofilm biomass by 36 %- 40 % relative to unexposed control. Consistently, biofilm mechanical stability (measured as Young's modulus) increased by 7.2-9.1 folds, and chemical stress resistance (measured with chlorine disinfection) increased by 1.4-2.0 folds. For P. aeruginosa, the minimal inhibitory concentration of different antibiotics also increased by 1.1-2.5 folds after combined exposure. Moreover, at a microbial community-wide level, metagenomic analysis revealed that the combined exposure enhanced the multi-species biofilm's resistance to chlorine, enriched the opportunistic pathogenic bacteria, and promoted their virulence and antibiotic resistance. Overall, the enhanced formation of biofilms (that may harbor opportunistic pathogens) by nanoplastics and background nanoparticles is an overlooked phenomenon, which may jeopardize the microbial safety of drinking water distribution systems.