Single-crystalline van der Waals layered dielectric with high dielectric constant.

The scaling of silicon-based transistors at sub-ten-nanometre technology nodes faces challenges such as interface imperfection and gate current leakage for an ultrathin silicon channel1,2. For next-generation nanoelectronics, high-mobility two-dimensional (2D) layered semiconductors with an atomic thickness and dangling-bond-free surfaces are expected as channel materials to achieve smaller channel sizes, less interfacial scattering and more efficient gate-field penetration1,2. However, further progress towards 2D electronics is hindered by factors such as the lack of a high dielectric constant (κ) dielectric with an atomically flat and dangling-bond-free surface3,4. Here, we report a facile synthesis of a single-crystalline high-κ (κ of roughly 16.5) van der Waals layered dielectric Bi2SeO5. The centimetre-scale single crystal of Bi2SeO5 can be efficiently exfoliated to an atomically flat nanosheet as large as 250 × 200 µm2 and as thin as monolayer. With these Bi2SeO5 nanosheets as dielectric and encapsulation layers, 2D materials such as Bi2O2Se, MoS2 and graphene show improved electronic performances. For example, in 2D Bi2O2Se, the quantum Hall effect is observed and the carrier mobility reaches 470,000 cm2 V-1 s-1 at 1.8 K. Our finding expands the realm of dielectric and opens up a new possibility for lowering the gate voltage and power consumption in 2D electronics and integrated circuits.

Comparative proteomic analysis of two divergent strains provides insights into thermotolerance mechanisms of Ganoderma lingzhi.

Heat stress (HS) is a major abiotic factor influencing fungal growth and metabolism. However, the genetic basis of thermotolerance in Ganoderma lingzhi (G. lingzhi) remains largely unknown. In this study, we investigated the thermotolerance capacities of 21 G. lingzhi strains and screened the thermo-tolerant (S566) and heat-sensitive (Z381) strains. The mycelia of S566 and Z381 were collected and subjected to a tandem mass tag (TMT)-based proteome assay. We identified 1493 differentially expressed proteins (DEPs), with 376 and 395 DEPs specific to the heat-tolerant and heat-susceptible genotypes, respectively. In the heat-tolerant genotype, upregulated proteins were linked to stimulus regulation and response. Proteins related to oxidative phosphorylation, glycosylphosphatidylinositol-anchor biosynthesis, and cell wall macromolecule metabolism were downregulated in susceptible genotypes. After HS, the mycelial growth of the heat-sensitive Z381 strain was inhibited, and mitochondrial cristae and cell wall integrity of this strain were severely impaired, suggesting that HS may inhibit mycelial growth of Z381 by damaging the cell wall and mitochondrial structure. Furthermore, thermotolerance-related regulatory pathways were explored by analyzing the protein-protein interaction network of DEPs considered to participate in the controlling the thermotolerance capacity. This study provides insights into G. lingzhi thermotolerance mechanisms and a basis for breeding a thermotolerant germplasm bank for G. lingzhi and other fungi.

Study on the inhibitory effect of fermentation extract of Microporus vernicipes on Candida albicans.

Candida albicans is one of the most common species of Candida, which cause various mucosal and systemic infectious diseases. However, the resistance rate to existing clinical antifungal drugs gradually increases in C. albicans. Therefore, new antifungal drugs must be developed to solve the current problem. This study discovered that the solid fermented ethyl acetate crude extract of Microporus vernicipes had inhibitory activity on C. albicans. This study determined that the Mv5 components had significantly inhibited the activity of C. albicans using column chromatography separation component screening. The components included 23 compounds of fatty acids and their derivatives, alkaloids, phenols, and other classes using ultra-high performance liquid chromatography tandem high-resolution mass spectrometry (UHPLC-HR-MS) analysis, with fatty acids constituting the primary components. The mechanism of action showed that the minimum inhibitory concentration (MIC) of Mv5 components against C. albicans was 15.63 µg/mL, while minimum fungicidal concentration (MFC) was 31.25 µg/mL. Mv5 components can inhibit the early biofilm formation and destroy the mature biofilm structure. It can inhibit the germ tube growth of C. albicans, thereby inhibiting the transformation of yeast morphology to hyphae. We detected 193 differentially expressed genes, including 156 upregulated and 37 downregulated genes in the Mv5 components of the MIC concentration group. We detected 391 differentially expressed genes, including 334 upregulated and 57 downregulated expression genes in the MFC concentration group. Among these differentially expressed genes, the genes related to mycelium and biofilm formation were significantly downregulated. GO enrichment analysis presented that single-organism process metabolic process, and cellular processes were the biological processes with the most gene enrichment. Kyoto Encyclopedia of Genes and Genomes (KEGG)of Mv5 components were mainly enriched in metabolic pathways, such as meiosis yeast and amino acid metabolism. Therefore, it is believed that the fermentation extract of M. vernicipes inhibits C. albicans, which can provide clues for developing effective antifungal drugs.

Hyaluronic acid-coated and Olaparib-loaded PEI - PLGA nanoparticles for the targeted therapy of triple negative breast cancer.

AIM: To prepare the hyaluronic acid-coated Olaparib-loaded PEI - PLGA nanoparticles (HA-Ola-PPNPs) and investigate their tumour-targeted anticancer effect. METHODS: The synthesis of HA-Ola-PPNPs was verified by DLS, TEM and SEM, followed was measured its cytotoxicity using CCK-8 assay. Confocal microscopy was used to observe the cellular uptake. Cell apoptosis was analysed by flow cytometry, biological SEM, and TEM. The expression of related proteins within the tumour site was investigated by immunostaining. RESULTS: The prepared HA-Ola-PPNPs showed a diameter of ∼160 nm with a negatively charged surface (-16.9 ± 2.7 mV) and sustained drug release behaviour. And the encapsulation efficiency of HA-Ola-PPNPs was 78.63 ± 5.29%. HA-Ola-PPNPs exhibited efficient in vitro and in vivo antitumor activities. HA-Ola-PPNPs induced cell apoptosis by upregulating Bax, Cytochrome C, and Caspase 3, downregulating Bcl-2 in breast cancer-bearing mice. CONCLUSIONS: According to the results, the Ola-loaded and HA-coated PEI - PLGA nanoparticles could be considered as a powerful tumour-targeted drug delivery system for TNBC treatment.

Caring ability of nursing students pre- and post-internship: a longitudinal study.

BACKGROUND: Nursing students' internship experiences may significantly impact their caring ability. However, there is a lack of comprehensive evaluation of undergraduate nursing students' caring ability pre-and post-internship in China. This study aimed to explore the differences in the caring ability of undergraduate nursing students before and after internship. METHODS: The sample comprised 305 undergraduate nursing students who had undergone internships during 2018-2020 in three hospitals in Changsha, China. Caring Ability Inventory was used to measure and compare nursing students' caring ability before and after internship. Descriptive statistics and paired t-test were employed to analyze data in SPSS software (version 22.0). RESULTS: A total of 300 students completed the survey (response rate = 98.37%). The overall score of caring ability and scores of cognitive and patience dimensions were higher after internship than before internship (P < 0.05). There was no significant improvement in the courage dimension (P > 0.05). CONCLUSIONS: Caring ability of undergraduate nursing students in China was at a low level, their overall caring ability significantly improved after the internship, indicating a positive relationship between internship and caring ability. Nursing educators and clinical nurses should emphasize the importance of caring ability development in internship planning and encourage nursing students to engage more with patients.

Inhibitory effect of triterpenoids from the mushroom Inonotus obliquus against α-glucosidase and their interaction: Inhibition kinetics and molecular stimulations.

Bioassay-guided fractionation led to the isolation of a series of triterpenoids (1-46) including 12 new ones (1-12) from the mushroom Inonotus obliquus. The structures of all the compounds were elucidated by spectroscopic analysis as well as by comparison with literature data. Triterpenoids 1-3, 6, 7, 16, 24, 25, 27, 38, 43, 44 and 46 showed strong α-glucosidase inhibition, with IC50 values from 11.5 to 81.8 µM. Their structure-activity relationships were discussed. Inonotusol F (24) showed the strongest inhibitory activity and it presented noncompetitive inhibition against α-glucosidase. Molecular docking and molecular dynamics stimulation further demonstrated that GLU302 and PHE298 were key amino acids for the inhibition of inonotusol F (24) towards α-glucosidase. This study indicates the vital role of triterpenoids in explaining hypoglycemic effect of Inonotus obliquus and provides important evidence for further development and utilization of this mushroom.

Hypouricaemic and nephroprotective effects of Poria cocos in hyperuricemic mice by up-regulating ATP-binding cassette super-family G member 2.

CONTEXT: Poria coco F.A.Wolf (Polyporaceae) dispels dampness and promotes diuresis implying hypouricaemic action. OBJECTIVE: To examine hypouricaemic action of Poria coco. MATERIALS AND METHODS: Ethanol extract (PCE) was prepared by extracting the sclerotium of P. cocos with ethanol, and the water extract (PCW) was produced by bathing the remains with water. PCE and PCW (50, 100 and 200 mg/kg, respectively) were orally administered to hyperuricemic Kunming mice (n = 8) to examine its hypouricaemic effect. Also, molecular docking was performed. RESULTS: P. cocos showed excellent hypouricaemic action, decreasing the serum uric acid of hyperuricaemia (HUA) control (526 ± 112 µmol/L) to 178 ± 53, 153 ± 57 and 151 ± 62 µmol/L (p < 0.01) by PCE and 69 ± 23, 63 ± 15 and 62 ± 20 µmol/L (p < 0.01) by PCW, respectively. According to SCrs, BUNs and H&E staining, PCE and PCW partially attenuated renal dysfunction caused by HUA. They presented no negative effects on ALT, AST and ALP activities. They elevated ABCG2 (ATP-binding cassette super-family G member 2) mRNA and protein expression in comparison to HUA control. In molecular docking, compound 267, 277, 13824, 15730 and 5759 were predicted as the top bioactives of P. cocos against HUA, which even presented better scores than the positive compound, oestrone 3-sulfate. DISCUSSION AND CONCLUSIONS: This paper demonstrated the hypouricaemic and nephroprotective effects of P. cocos in hyperuricemic mice by up-regulating ABCG2. These results may be useful for the development of a hypouricaemic agent.

Pharmacy administration and pharmaceutical care practice in a module hospital during the COVID-19 epidemic.

OBJECTIVES: To describe the pharmacy administration and pharmaceutical care in a module hospital during the coronavirus disease 2019 (COVID-19) epidemic and provide reference for domestic and foreign pharmacists participating in the epidemic prevention and control. SETTING: The study was performed in a Jianghan module hospital constructed at the Wuhan Convention and Exhibition Center in Wuhan, China. This is 1 of the first 3 module hospitals. PRACTICE DESCRIPTION: One thousand eight hundred forty-eight patients were admitted to the Jianghan module hospital, and 1327 cases (71.81% of the total number) were cured and discharged. Pharmacists have successfully completed the tasks of purchase, storage, and free distribution of drugs worth ¥1.03 million (approximately $146,000), reviewed about 20,000 electronic orders, provided one-on-one online medication consultation for 484 patients, and held 5 lectures on rational drug use knowledge, which could help reduce irrational drug use and minimize the risk involved. PRACTICE INNOVATION: The new COVID-19 "module" pharmaceutical care model is equipped with new features such as pharmacy emergency command group, organizational structure for pharmacy administration, electronic control of drug prescription, and "zero contact" pharmaceutical care relying on the new media platform "WeChat." This platform provides relevant pharmaceutical care for patients, such as ensuring drug supply, setting up critical care drug trolleys, designing specific drug packaging bags, creating a module radio station to broadcast rational drug use information to the patients, and other aspects. EVALUATION: With the continuous improvement of the module hospital and the progress in in-depth knowledge about COVID-19, some aspects such as patient admission criteria and variety of drugs need to be adjusted depending on the actual situation. RESULTS: The pharmacists provided pharmaceutical care for 1848 patients with mild COVID-19 disease. They not only ensured the timely supply of the drugs but also reduced the incidence of drug-induced risks through medication review and guidance, thereby improving patient compliance and helping the patients rebuild their confidence in overcoming the disease. CONCLUSION: The new COVID-19 module pharmaceutical care model has played an important role in overcoming the epidemic situation of COVID-19 in China and thus can be implemented on a broader scale.

Orientation-Controlled 2D Anisotropic and Isotropic Photon Transport in Co-crystal Polymorph Microplates.

2D anisotropic transport of photons/electrons is crucial for constructing ultracompact on-chip circuits. To date, the photons in organic 2D crystals usually exhibit the isotropic propagation, and the anisotropic behaviors have not yet been fully demonstrated. Now, an orientation-controlled photon-dipole interaction strategy was proposed to rationally realize the anisotropic and isotropic 2D photon transport in two co-crystal polymorph microplates. The monoclinic microplate adopts a nearly horizontal transition dipole moment (TDM) orientation in 2D plane, exhibiting anisotropic photon-dipole interactions and thus distinct re-absorption waveguide losses for different 2D directions. By contrast, the triclinic plate with a vertical TDM orientation, shows 2D isotropic photon-dipole interactions and thus the same re-absorption losses along different directions. Based on this anisotropy, a directional signal outcoupler was designed for the directional transmission of the real signals.

Synthesis, purification, and anticancer effect of magnetic Fe3O4-loaded poly (lactic-co-glycolic) nanoparticles of the natural drug tetrandrine.

Here, we have successfully synthesised and purified multifunctional PLGA-based nanoparticles by the co-encapsulation of an anticancer drug (tetrandrine) and a magnetic material (Fe3O4). The obtained Tet-Fe3O4-PLGA NPs had a uniform spherical shape with a particle size of approximately 199 nm and a negative surface charge of -18.0 mV, displaying a high encapsulation efficiency. Furthermore, TEM studies provided representative images of the purification process of the magnetic nanoparticles with MACS® technology. The MFM and VSM results indicated that both the Fe3O4 NPs and Tet-Fe3O4-PLGA NPs were superparamagnetic. The DSC spectrum demonstrated that Tet was successfully encapsulated within the PLGA-based nanoparticles. Significantly, the release studies revealed NPs had a relatively slower release rate than free Tet after 8 h's initial burst release, which had decreased from 98% to 65% after 24 h. In vitro cellular studies revealed that NPs could effectively penetrate into A549 cells and A549 multicellular spheroids to exert cytotoxicity, displaying a significantly high anti-proliferation effect. Moreover, western blot demonstrated that the co-loaded NPs had a higher anticancer activity by injuring lysosomes to activate the mitochondria pathway and induce A549 cell apoptosis. The magnetic characteristics and high anticancer activity support the use of Tet/Fe3O4 co-loaded PLGA-based nanoparticles as a promising strategy in the treatment of lung cancer.

Actions of Inonotus obliquus against Hyperuricemia through XOD and Bioactives Screened by Molecular Modeling.

Inonotus obliquus is an edible mushroom and also a remedy against various diseases, especially metabolic syndrome. In this paper we report the actions of an ethanol extract of I. obliquus (IOE) against hyperuricemia in hyperuricemic mice, and the screen of bioactives. The extract (IOE) was prepared by extracting I. obliquus at 65 °C with ethanol, and characterized by HPLC. IOE at low, middle, and high doses reduced serum uric acid (SUA) of hyperuricemic mice (353 µmol/L) to 215, 174, and 152 µmol/L (p < 0.01), respectively, showing similar hypouricemic effectiveness to the positive controls. IOE showed a non-toxic impact on kidney and liver functions. Of note, IOE suppressed xanthine oxidase (XOD) activity in serum and liver, and also down-regulated renal uric acid transporter 1 (URAT1). Four compounds hit highly against XOD in molecular docking. Overall, the four compounds all occupied the active tunnel, which may inhibit the substrate from entering. The IC50 of betulin was assayed at 121.10 ± 4.57 µM, which was near to that of allopurinol (148.10 ± 5.27 µM). Betulin may be one of the anti-hyperuricemia bioactives in I. obliquus.

Resurfaced fluorescent protein as a sensing platform for label-free detection of copper(II) ion and acetylcholinesterase activity.

Protein engineering by resurfacing is an efficient approach to provide new molecular toolkits for biotechnology and bioanalytical chemistry. H39GFP is a new variant of green fluorescent protein (GFP) containing 39 histidine residues in the primary sequence that was developed by protein resurfacing. Herein, taking H39GFP as the signal reporter, a label-free fluorometric sensor for Cu(2+) sensing was developed based on the unique multivalent metal ion-binding property of H39GFP and fluorescence quenching effect of Cu(2+) by electron transfer. The high affinity of H39GFP with Cu(2+) (Kd, 16.2 nM) leads to rapid detection of Cu(2+) in 5 min with a low detection limit (50 nM). Using acetylthiocholine (ATCh) as the substrate, this H39GFP/Cu(2+) complex-based sensor was further applied for the turn-on fluorescence detection of acetylcholinesterase (AChE) activity. The assay was based on the reaction between Cu(2+) and thiocholine, the hydrolysis product of ATCh by AChE. The proposed sensor is highly sensitive (limit of detection (LOD) = 0.015 mU mL(-1)) and is feasible for screening inhibitors of AChE. Furthermore, the practicability of this method was demonstrated by the detection of pesticide residue (carbaryl) in real food samples. Hence, the successful applications of H39GFP in the detection of metal ion and enzyme activity present the prospect of resurfaced proteins as versatile biosensing platforms.

Automatic and integrated micro-enzyme assay (AIµEA) platform for highly sensitive thrombin analysis via an engineered fluorescence protein-functionalized monolithic capillary column.

Nowadays, large-scale screening for enzyme discovery, engineering, and drug discovery processes require simple, fast, and sensitive enzyme activity assay platforms with high integration and potential for high-throughput detection. Herein, a novel automatic and integrated micro-enzyme assay (AIµEA) platform was proposed based on a unique microreaction system fabricated by a engineered green fluorescence protein (GFP)-functionalized monolithic capillary column, with thrombin as an example. The recombinant GFP probe was rationally engineered to possess a His-tag and a substrate sequence of thrombin, which enable it to be immobilized on the monolith via metal affinity binding, and to be released after thrombin digestion. Combined with capillary electrophoresis-laser-induced fluorescence (CE-LIF), all the procedures, including thrombin injection, online enzymatic digestion in the microreaction system, and label-free detection of the released GFP, were integrated in a single electrophoretic process. By taking advantage of the ultrahigh loading capacity of the AIµEA platform and the CE automatic programming setup, one microreaction column was sufficient for many times digestion without replacement. The novel microreaction system showed significantly enhanced catalytic efficiency, about 30 fold higher than that of the equivalent bulk reaction. Accordingly, the AIµEA platform was highly sensitive with a limit of detection down to 1 pM of thrombin. Moreover, the AIµEA platform was robust and reliable to detect thrombin in human serum samples and its inhibition by hirudin. Hence, this AIµEA platform exhibits great potential for high-throughput analysis in future biological application, disease diagnostics, and drug screening.

Facile and robust dual interaction modification of hexadecyldimethyl amine magnetic nanoparticles for the ultrasensitive analysis of perfluorinated compounds in environmental water.

In this work, a novel extraction and enrichment technique based on hexadecyldimethyl amine functionalized magnetic nanoparticles has been successfully developed for the preconcentration and ultrasensitive detection of perfluorinated compounds in environmental water samples with high-performance liquid chromatography coupled with tandem triple quadrupole mass spectrometry. As a novel surfactant, hexadecyldimethyl amine functionalized on magnetic nanoparticles was realized through one-step facile and robust quaterization reaction, greatly superior to previous multiple-step and unstable modification. The functional nanoparticles of homogeneous nanospheres and excellent magnetic properties were characterized with scanning electron microscopy, X-ray diffraction patterns, Fourier transform infrared spectroscopy, and vibrating sample magnetometry. Dual mechanisms of both hydrophobic and electrostatic interactions were simultaneously introduced for anionic perfluorinated compounds effective enrichment. Under optimized extraction conditions, satisfactory precision and accuracy for anionic perfluorinated compounds analysis were achieved with good linear ranging from 0.5 to 20 ng/L, as well as fascinating sensitivity with low limits of detection up to 3.0 × 10(-2) -5.0 × 10(-2) ng/L. High preconcentration efficiency and extraction recoveries ranged from 81.04-103.2% with relative standard deviations (n = 5) less than 10% have also been realized. Thereby, our proposed method is convenient and efficient for enrichment, exhibiting good application prospect in future environmental perfluorinated compounds analysis.

[Effect of reinforced health education on deep radiofrequency thermotherapy for patients with tumor].

OBJECTIVE: To explore the effect of reinforced health education on deep radiofrequency thermotherapy for patients with tumor. METHODS: From June 2012 to June 2014, 106 patients who underwent deep radiofrequency thermotherapy in our hospital were randomly selected, and were divided into a control group (n=69) and an observation group (n=65). The observation group received reinforced health education while the control group received the traditional health education before treatment. Th e reinforced health education included preparation, cooperation and health behavior during and aft er treatment. Th en the compliance rate, degree of satisfaction, and the awareness rate of related knowledge were compared and analyzed aft er treatment between the 2 groups. RESULTS: Th e compliance rate in the observation group and the control group was 85.51% and 63.08% respectively; there was significant difference in the awareness rates of related knowledge and the overall degree of satisfaction between the patients and their family members (all P<0.05). CONCLUSION: Implement of reinforced health education is benefit to patients to understand the content of health education before treatment and keep health behavior after treatment, and can also improve the compliance, the degree of satisfaction in the deep radiofrequency thermotherapy for patients with tumor.

Natural cotton fibers as adsorbent for solid-phase extraction of polycyclic aromatic hydrocarbons in water samples.

A natural material, cotton fiber, has been applied as a solid-phase extraction (SPE) adsorbent for sample preparation for the analysis of polycyclic aromatic hydrocarbons (PAH) in water samples using high-performance liquid chromatography. The cotton fiber was used directly without any chemical modifications, which avoided a complex synthesis process and consumption of a large volume of organic solvent. The conditions affecting the extraction efficiency were optimized to achieve high detection sensitivity, and included elution solvent, ultrasonic elution time, extraction time, sample volume, salt concentration and organic modifier addition. Under the optimal conditions, the detection limits for seven PAH compounds could reach up to 0.1-2.0 ng L(-1). The method accuracy was evaluated using recovery measurements in standard spiked samples and good recoveries of 70.69-110.04% with relative standard deviations of less than 10% have been achieved. Consequently, the method developed was successfully applied for determining PAH in environmental samples: snow water, metal-fabrication factory wastewater and Xiangjiang River water, with PAH contents ranging from 13.2 to 83.1 ng L(-1). Therefore, using cotton fiber as a new SPE adsorbent, was easy to prepare, had a low cost and great reusability, and this implies it is a promising method for sample preparation.

Two novel zeolitic imidazolate frameworks (ZIFs) as sorbents for solid-phase extraction (SPE) of polycyclic aromatic hydrocarbons (PAHs) in environmental water samples.

In this work, two novel zeolitic imidazolate framework (ZIF) materials, ZIF-7 and ZIF-11, were firstly introduced as solid-phase extraction (SPE) sorbents for PAHs efficient extraction and highly sensitive analysis in environmental water samples with high performance liquid chromatography (HPLC) coupled with fluorescence detection. ZIF-7 and ZIF-11 were successfully synthesized and characterized with SEM, FTIR, XRD and water contact angels, exhibiting unique and excellent stability, spatial structure and chemical composition, promising for environmental PAHs efficient enrichment through hydrophobic, π-π and π-complexation interactions. The topology effect on PAHs extraction was compared between ZIF-7 and ZIF-11, considering they have the same composition in metal ion (Zn(2+)) and organic linker, but differing spatial structures: ZIF-7 has a cubic structure, while ZIF-11 is a rhombic dodecahedron. At last, ZIF-11 with markedly better extraction efficiencies was selected for subsequent analysis. Under optimum extraction conditions such as sample volume, extraction time, desorption conditions, volume of organic modifier and salt concentration, a robust and highly efficient method based on ZIF-11 as a novel SPE sorbent has been successfully developed for environmental PAHs analysis. Satisfactory precision and accuracy ranging from 1-2.4 × 10(3) ng L(-1) as well as ultrasensitive detection limits of 0.08-1.6 ng L(-1) have been successfully achieved. Moreover, ZIF-11 extraction also exhibited high recoveries of 82.4-112.7% with relative standard deviations (RSDs) being less than 9% for PAHs in the environmental water samples. Therefore, our novel, convenient and efficient extraction method based on ZIF-11 as a sorbent is promising for applications in future trace-level environmental PAHs analyses.

Lithium fluorosulfonate-induced low-resistance interphase boosting low-temperature performance of commercial graphite/LiFePO4 pouch batteries.

The performance of Li-ion batteries (LIBs) at sub-ambient temperatures is limited by the resistive interphases due to electrolyte decomposition, particularly on the anode surface. In this study, lithium fluorosulfonate (LFS) was added to commercial electrolytes to enhance the low-temperature electrochemical performance of LiFePO4 (LFP)/graphite (Gr) pouch cells. The addition of LFS significantly reduced the charge transfer resistance of the anode, substantially extending the cycle life and discharge capacity of commercial LFP/Gr pouch cells at -10 and -30 °C. Compared with the capacity retention rate of the baseline electrolyte at -10 °C (80 % after 25cycles), the capacity retention rate of the LFS electrolyte after 100 cycles under 0.5 C/0.5 C was retained at 94 %. Further mechanistic studies showed that the LFS additive induced the formation of a solid electrolyte interphase (SEI) film comprising inorganic-rich LiF, Li2SO4, and additional organic fluorides and sulfides to maintain good stability at the Gr/electrolyte interface during low-temperature operation. LFS suppressed electrolyte decomposition by forming a robust and low-resistance SEI film on the anode. These results demonstrate that LFS is a promising electrolyte additive for low-temperature LFP/Gr pouch cells.

Hepatitis-related adverse events associated with immune checkpoint inhibitors in cancer patients: an observational, retrospective, pharmacovigilance study using the FAERS database.

Background: Immune checkpoint inhibitors (ICIs), including anti-PD-1, anti-PD-L1 and anti-CTLA-4 antibodies, have become a standard treatment for multiple cancer types. However, ICIs can induce immune-related adverse events, with hepatitis-related adverse events (HRAEs) being of particular concern. Our objective is to identify and characterize HRAEs that exhibit a significant association with ICIs using real-world data. Methods: In this observational and retrospective pharmacovigilance study, we extracted real-world adverse events reports from the FDA Adverse Event Reporting System database spanning from the first quarter of 2004 to the first quarter of 2023. We conducted both Frequentist and Bayesian methodologies in the framework of disproportionality analysis, which included the reporting odds ratios (ROR) and information components (IC) to explore the intricate relationship between ICIs and HRAEs. Results: Through disproportionality analysis, we identified three categories of HRAEs as being significantly related with ICIs, including autoimmune hepatitis (634 cases, ROR 19.34 [95% CI 17.80-21.02]; IC025 2.43), immune-mediated hepatitis (546 cases, ROR 217.24 [189.95-248.45]; IC025 4.75), and hepatitis fulminant (80 cases, ROR 4.56 [3.65-5.70]; IC025 0.49). The median age of patients who report ICI-related HRAEs was 63 years (interquartile range [IQR] 53.8-72), with a fatal outcome observed in 24.9% (313/1,260) of these reports. Cases pertaining to skin cancer, lung cancer, and kidney cancer constituted the majority of these occurrences. Patients treated with anti-PD-1 or anti-PD-L1 antibodies exhibited a higher frequency of immune-mediated hepatitis in comparison to those undergoing anti-CTLA-4 monotherapy, with a ROR of 3.59 (95% CI 1.78-6.18). Moreover, the dual ICI therapy demonstrated higher reporting rates of ICI-related HRAEs compared to ICI monotherapy. Conclusion: Our findings confirm that ICI treatment carries a significant risk of severe HRAEs, in particular autoimmune hepatitis, immune-mediated hepatitis, and hepatitis fulminant. Healthcare providers should exercise heightened vigilance regarding these risks when managing patients receiving ICIs.

Pulmonary haemorrhage and haemoptysis associated with bevacizumab-related treatment regimens: a retrospective, pharmacovigilance study using the FAERS database.

Background: Bevacizumab (BV) is widely used in routine cancer treatment and clinical therapy in combination with many other agents. This study aims to describe and analyse post-market cases of pulmonary haemorrhage and haemoptysis reported with different BV treatment regimens by mining data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: Data were collected from the FAERS database between 2004 Q1 and 2023 Q1. Disproportionality analysis including the reporting odds ratio (ROR) was employed to quantify the signals of disproportionate reporting of pulmonary haemorrhage and haemoptysis adverse events (AEs) associated with BV-related treatment regimens. The demographic characteristics, time to onset and outcomes were further clarified. Results: A total of 55,184 BV-associated reports were extracted from the FAERS database, of which 497 reports related to pulmonary haemorrhage and haemoptysis. Overall, the median onset time of pulmonary haemorrhage and haemoptysis AEs was 43 days (interquartile range (IQR) 15-117 days). In the subgroup analysis, BV plus targeted therapy had the longest median onset time of 90.5 days (IQR 34-178.5 days), while BV plus chemotherapy had the shortest of 40.5 days (IQR 14-90.25). BV plus chemotherapy disproportionately reported the highest percentage of death (148 deaths out of 292 cases, 50.68%). Moreover, the BV-related treatments including four subgroups in our study demonstrated the positive signals with the association of disproportionate reporting of pulmonary haemorrhage and haemoptysis. Notably, BV plus chemotherapy showed a significant higher reporting risk in pulmonary haemorrhage and haemoptysis signals of disproportionate reporting in comparison to BV monotherapy (ROR 5.35 [95% CI, 4.78-6.02] vs. ROR 4.19 [95% CI, 3.56-4.91], p = 0.0147). Conclusion: This study characterized the reporting of pulmonary haemorrhage and haemoptysis, along with the time to onset and demographic characteristics among different BV-related treatment options. It could provide valuable evidence for further studies and clinical practice of BV.