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Layered spherical aggregates of melamine cyanurate complex (MCA) were self-assembled on the surface of α-zirconium phosphate and an inorganic-organic composite flame retardant α-zirconium phosphate@melamine cyanurate (AMC) was synthesized via a facile way. The influences of AMC on the thermal, mechanical, and flame retardancy of intumescent flame-retardant polypropylene (PP) system were studied. The results indicated that the addition of AMC could enhance the thermal stability of PP composites, and increase the final amount of char residue. The kinetics studies indicated that more activation energy of degradation was necessary when combined with AMC. Flame-retardant tests revealed that 2 wt% loading of AMC with 24 wt% intumescent flame retardant (IFR) could impart PP composites with the highest values of LOI, reached 31.2%, and passed the UL-94 V-0 rating. Without the MCA shell, the LOI of PP composites decreased to 27.1% and the V-1 rating was obtained. The existence of MCA shell reinforced the synergistic effect between α-ZrP core and IFR. The investigation of char residues indicates that AMC could not only enhance the amount, but also the graphitization of char layer, including physically strengthened effect. In the end, the mechanical properties were investigated as well. [ABSTRACT FROM AUTHOR]

A heat-resistant boehmite-coated polypropylene (PP) membrane has been successfully fabricated and its potential application as a promising separator in the lithium-ion battery was explored. The boehmite powders with average sizes of 0.78, 1.03, and 1.72 μm, respectively, were used to fabricate the coated membrane. It was demonstrated that the coated membrane prepared by boehmite with a 0.78-μm size showed superior heat tolerance and proper air permeability. As compared to the commercialized PP membrane, such coated membrane presented improved electrolyte uptake, better interface stability, and enhanced ionic conductivity. In addition, the lithium iron phosphate (LiFePO4)/Li cell using this composite membrane exhibited better rate capability and cycling retention than that using PP membrane owing to its facile ion transport and excellent interfacial compatibility. The coating layer showed an advantage on solid electrolyte interface film formation and greatly reduced charge transfer resistance. All these fascinating characteristics would boost the application of this composite membrane for high-performance lithium-ion battery. [ABSTRACT FROM AUTHOR]

The article focus on solving quarter-plane lattice walks with interactions via the kernel method. Topics include number of n-step paths that start at point which visit vertices on the horizontal boundary; and how interactions will affect the solubility of quarter-plane lattice walk models and the properties of the generating functions Q(x, y, t).

To improve the strength and modulus of polypropylene (PP) microporous membrane, the nano-silicon dioxide (SiO2) was introduced and the influence of SiO2 content on the structure and properties of initial precursor film and stretched microporous membrane was investigated. It was found that with increasing SiO2 content to 2%, the crystalline orientation degree of precursor film was decreased from 0.41 to 0.32, but the elastic recovery value did not change much. The mean pore diameter of the stretched microporous membrane was increased from 28.3 to 32.5 nm. The Gurley value (characterizing the air permeability) only decreased from 200 to 194 s. The tensile strength and elastic modulus were increased by 33.3 and 72.0 MPa, respectively. But when the SiO2 content was 10%, the air permeability of stretched microporous membrane was apparently decreased by 21.5%. Compared with that of microporous membrane without SiO2, the tensile strength was increased by only 1.6 MPa. It was concluded that the introduction of 2% content of SiO2 resulted in the improvement of mechanical properties, at the same time did not deteriorate the pore structure and properties of PP microporous membrane. POLYM. COMPOS., 37:2684-2691, 2016. © 2015 Society of Plastics Engineers [ABSTRACT FROM AUTHOR]

Although activated carbon is an effective tool for adsorbing phenolic compounds, it has not been systematically studied in the adsorption of phenolic compounds in the multi-component solutions. Adsorption characteristics and kinetics of phenol,o-, m-, p-cresol, catechol, hydroquinone, and resorcinol onto granular activated carbon were examined in single- and multi-component solutions. Results indicated that the adsorption rate constants decreased in the order ofp-cresol >o-cresol > catechol > resorcinol >m-cresol > hydroquinone > phenol in single-component solutions. The pseudo-second-order model was better than the pseudo-first-order model for fitting the experimental data in the multi-component solutions. The adsorption rate constants of dihydric phenols isomers decreased dramatically when the solutions contained phenol and cresol isomers. Resorcinol exhibited a significant promoting effect on adsorption capacities of cresol isomers. The adsorption capacities almost obeyed the following sequence of (catechol, hydroquinone) > cresol isomers > (resorcinol, phenol) in the multi-component solutions. The distribution constants (bi) of phenol were 3.169, 3.175, and 3.249, respectively, in the ternary solutions, which were significantly higher than the values of other two components (No. 1,o-cresol 2.951, catechol 2.893; No. 2,o-cresol 2.864, resorcinol 2.977; No. 3,o-cresol 2.918, hydroquinone 2.861). Results also demonstrated the solubility and functional groups of phenolic compounds might play a key role in their competitive adsorption capabilities in multi-component solutions. [ABSTRACT FROM PUBLISHER]

Polyvinylidene fluoride (PVDF) film samples were prepared by extrusion casting followed by annealing. Then, the samples were uniaxially cold stretched at room temperature, followed by uniaxial hot stretching. The total uniaxial stretching ratio of the samples after cold and hot stretching steps was kept constant at 100%. The influence of hot-stretching temperatures and cold and hot stretching ratios on the crystal transformation and pore structure was investigated using wide-angle X-ray diffraction(WAXD), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). The results showed that the stretching-induced β-phase content did not depend on hot stretching temperature and cold and hot stretching ratios. Apparent connecting bridge structure between the separated lamellae was observed at 130℃ stretching temperature and 40% to 60% or 50% to 50% cold and hot stretching ratio. Compared with that induced by cold stretching alone, more connecting bridges were formed and higher β-phase concentration was created by cold stretching followed by hot stretching. During hot stretching, some imperfect chains from main lamellae were stretched and converted to part connecting bridges, and some other imperfect chains were transformed to the β-phase. But, the β-phase content during hot stretching was not related to the extent of connecting structure. [ABSTRACT FROM PUBLISHER]

The polyvinylidene fluoride cast film was prepared with different melt-draw ratios by a cast extrusion process. The structure and properties of the prepared films were characterized by differential scanning calorimetry, X-ray diffraction, Fourier transform infrared and scanning electrical microscopy. The results showed that with increasing melt-draw ratio, the crystalline orientation increased and the crystalline morphology transformed from spherulites to parallel lamellae perpendicular to the extrusion direction. At the same time, necking behavior in the stress–strain curves disappeared and strain-hardening behavior became apparent. The lamellae thickness distribution became uniform. The polarized Fourier transform infrared results also indicated the existence of some β-phase for the samples with different melt-draw ratios. [ABSTRACT FROM PUBLISHER]

ABSTRACT The crystalline morphology and microstructure during stretching of polyvinylidene fluoride hard elastic film under room temperature was followed using wide-angle X-ray diffraction (WAXD), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). It was found that an endotherm plateau from the contribution of some new crystals formed during annealing appeared and some thinner lamellae existed in the annealed film. During stretching, the endotherm plateau disappeared and those thinner lamellae transformed into β-phase. At the same time, some initial pores were observed. With increasing stretching ratio from 20 to 100%, the β-phase content increased, whereas within the strain rate range of 0.003-0.034 s−1, its content was least under 0.017 s−1. During stretching, lamellae separation, crystalline morphology transformation and disappearance of grown crystals formed by annealing coexisted. From the viewpoint of pore initiation, less crystalline morphology transformation was beneficial for the lamellae separation. Higher stretching ratio resulted in the breakage of separated lamellae. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40077. [ABSTRACT FROM AUTHOR]

Heishunpian is obtained through complex processing of Aconiti lateralis radix praeparata. However, the impact of each processing step on chemical compositions and pharmacological activities is still unclear. The mechanism of the processing needs to be further studied. The samples were all prepared using the "step knockout" strategy for UPLC-QTOF-MS analysis, and analgesic and anti-inflammatory efficacy evaluation. Each sample was analyzed by UPLC-QTOF-MS to determine the component differences. The hot plate test and acetic acid writhing test were used to evaluate the analgesic effect. Anti-inflammatory efficacy was evaluated by xylene-induced ear edema test. The correlation between components and efficacies was studied to screen the effective components for further investigating the processing of Heishunpian. Mass spectrum analysis results showed that 49 components were identified, and it appeared that brine immersion and rinsing had a great influence on the components. In the hot plate test, ibuprofen and Heishunpian had the most significant effect, while ibuprofen and the sample without rinsing showed the best efficacy for the acetic acid writhing test. The sample without dyeing had the best effect on ear edema. The correlation analysis indicated that mesaconine, aconine, 3-deoxyaconine, delbruine, and asperglaucide were potentially considered effective analgesic components. It is not recommended to remove brine immersion and rinsing. Boiling and steaming are necessary processes that improve efficacy. Dyeing, which does not have a significant impact on components and efficacy, may be an unnecessary process. This research has been of great significance in identifying anti-inflammatory and analgesic components and optimizing processing for Heishunpian. [Display omitted] • The dyeing process of Aconiti lateralis radix praeparata for beauty may affect the efficacy. • C-1 and C-6 methoxyl and C-13 and C-15 hydroxyl may be analgesic active groups of alcohol amine alkaloids. • Mesaconine, aconine, and 3-deoxyaconine have different analgesic mechanisms compared to delbruine and asperglaucide. [ABSTRACT FROM AUTHOR]

• New generation polymer gel electrolytes are fabricated by PVDF-PU. • Preparation of pore composite membranes by solution casting phase separation method. • The β phase in PVDF exhibits excellent polarization effects. • PU enhances the electrochemical stability and tensile properties of the electrolyte. • The composite polymer electrolytes demonstrate excellent coulombic efficiency. The β-phase in polyvinylidene fluoride (PVDF) exhibits superior dielectric properties as compared to α-phase, with ionic conductivity in liquid electrolytes up to one magnitude higher than that of α-phase, providing excellent ion transportation performance when applied as polymer gel electrolytes (GPEs). However, the strong polarization effect affects the electrochemical stability of GPEs. To improve the electrochemical stability while maintaining high ionic conductivity, PVDF and PU are selected to be co-blended. Porous polymer membranes containing polar β phase are prepared by solution-casting phase separation, and then swollen and activated in the electrolyte to obtain PVDF-PU composite GPEs. The results show that PVDF 0.8 -PU 0.2 GPE exhibits an ionic conductivity of 8.81 × 10-4 S cm−1 at room temperature and 1.88 × 10-3 S cm−1 at 65 °C (the polyether segment in PU starts to melt). Li+ transference numbers (∼0.84), electrochemical oxidation limit (∼4.3 V) and charge–discharge performance satisfy the commercial requirements. Coulombic efficiency (∼99%) and capacity retention (∼96%) indicate that this GPE promises to be commercially available. [ABSTRACT FROM AUTHOR]

Recently, the battery security issue receives widespread attention. Investigating the compression performance and failure mode of the battery separator, and then simulating the internal soft short-circuit of the battery due to separator rupture becomes the current focus. In this work, commercial polyethylene separators are coated with a Al 2 O 3 composite organic silicone - acrylic acid gel layer and the electrochemical performance are characterized. The coated battery separator (PEAE-5) exhibits the lowest charge transfer resistance and increases the electrochemical stability window to 5.3 V, since the silicone exhibits oxidation resistance and the acrylic provides flexibility in polar electrolyte solvents. Subsequently, the battery separator is punched in cycles to simulate fatigue failure of the separator under external compression. The results indicate that the separator (PEAE-5) coated with a 5% solid content of organic silicone - acrylic acid emulsion exhibits the best combined physical-mechanical and electrochemical properties, maintaining nearly 80% of the original cycling performance after 50 cycles of compression. The separator coated with the composite organic silicone - acrylic acid gel layer suffers the least from cycle fatigue. The existence of the flexible gelatinous coating layer affords an efficient method to protect the battery separator from destruction. [Display omitted] [ABSTRACT FROM AUTHOR]

High-performance PBS films can be prepared by the melt-stretching method. The effect of the melt-drawing ratio (MDR) on the mechanical properties and microstructure of PBS cast films prepared by melt-stretching is studied in this paper. The elastic modulus, tensile stress, and strain hardening increase with increasing MDR. With an MDR of 25–50, the crystalline morphology changes from deformed spherulites to row-nucleated lamellar structure. The lateral size and orientation of the lamellae apparently improve with the MDR. When the MDR is within 50–125, the row-nucleated lamellar structure improves slightly by increasing the lateral size and orientation of the lamellae. The component fraction and thickness of the mobile (MAF) and rigid (RAF) amorphous fractions and crystalline phase are nearly unchanged within the whole MDR range. The increases in lateral size and orientation improve the mechanical properties of the films. Significantly, the linear relationship between the elastic modulus and orientation at MDRs from 50 to 125 indicates that the elastic modulus is determined by the crystal orientation in PBS cast films with row-nucleated lamellae. This work evaluates the importance of orientation for microstructure and properties of PBS films, which may guide the processing of high-performance PBS films. 1. High-performance PBS films can be prepared by the melt-stretching method. 2. The increases in lateral size and orientation improve the mechanical properties of the PBS films with the change of MDR. 3. The elastic modulus is determined by the crystal orientation in cast PBS films with row-nucleated lamellae. [ABSTRACT FROM AUTHOR]

The fluorescent probes with good water-solubility, long-wavelength emission and large Stokes shift are greatly desirable for in vivo detection. Herein, we designed a novel 1,8-naphthalimide-based near-infrared (NIR) optical and fluorescent probe (NTC) for sensing cysteine (Cys). Using acrylate as the recognition site, the probe demonstrated high selectivity and sensitivity for Cys with a low detection limit (0.093 μM) in aqueous buffer solution due to the excellent water-solubility. Upon the reaction with Cys, the recovery of intramolecular charge transfer (ICT) in the probe led to about 40-fold fluorescence enhancement. Furthermore, the reaction result was investigated by 1H NMR, and HRMS analyses, and the sensing mechanism was validated by quantum calculations. Finally, NTC was applied to image exogenous and endogenous Cys in HeLa cells and zebrafish selectively, implying that the probe possessed great potential application in biological fluorescence sensing. Unlabelled Image • A new colorimetric and fluorescent probe (NTC) based on polycyano-naphthalimide is designed for detecting Cys over Hcy and GSH. • The probe exhibits high sensitivity and selectivity, excellent water solubility, NIR emission and large Stokes shift. • The sensing mechanism is investigated by 1H NMR, HRMS analyses and DFT calculations. • The probe is successfully applied to monitoring of exogenous and endogenous Cys in living cells and zebrafish. [ABSTRACT FROM AUTHOR]

• A self-healable and recyclable silicone elastomer realized by UV/thermo curing. • Self-healing and recycling abilities derived from reversible ionic crosslinks. • The silicone elastomer was transparent and hydrolysis-resistant. • The silicone elastomer could be 3D printed into self-healable soft devices. Various intrinsic self-healing silicone elastomers have been developed by incorporating different dynamic noncovalent or covalent bonds into elastomeric crosslinked networks. However, these self-healable silicone elastomers are either nontransparent or nonresistant to hydrolysis. In this study, a transparent and hydrolysis-resistant silicone elastomer with self-healability, reprocessability and 3D printability is facilely fabricated by successively thiol-ene UV-curing between thiol and vinyl functionalized polysiloxanes, and thermocuring between carboxyl and amido functionalized polysiloxanes. These obtained elastomers show an excellent healing efficiency of 97%, and the healing processes are repeatable for many times. Moreover, these elastomers can be repeatedly reprocessed with a recovery of 90% of virgin mechanical strengths, and the reprocessed elastomers can still repair damages with an efficiency over 90%. These self-healing and reprocessing behaviors mainly derive from the rearrangement of crosslinked networks via reversible breakage and reformation of ionic bonds. Importantly, the silicone elastomers are transparent with a transmittance of over 90% in visible light and hydrolysis-resistant to hydro-thermal treatment. Besides, the silicone elastomers can be fabricated into various self-healable architectures via 3D printing. Therefore, a feasible approach is provided to impart reversible ionic association induced self-healing and reprocessing to 3D printable silicone elastomers. [ABSTRACT FROM AUTHOR]

Introduction: One of the methods for pain management involves the use of local anesthesia, which numbs sensations in specific body regions while maintaining consciousness., Objectives: Considering the certain limitations (e.g., pain, the requirement of skilled professionals, or slow passive diffusion) of conventional delivery methods of local anesthetics, developing alternative strategies that offer minimally invasive yet therapeutically effective delivery systems is of great concern for ophthalmic regional anesthesia., Methods and Results: In this study, a rapidly dissolving cambered microneedle (MNs) patch, composed of poly(vinylpyrrolidone) (PVP) and hyaluronic acid (HA) and served as a delivery system for lidocaine (Lido) in local anesthesia, was developed taking inspiration from the mosquito proboscis's ability to extract blood unnoticed. The lidocaine-containing MNs patch (MNs@Lido) consisted of 25 microneedles with a four-pronged cone structure (height: 500 μm, base width: 275 μm), arranged in a concentric circle pattern on the patch, and displays excellent dissolubility for effective drug delivery of Lido. After confirming good cytocompatibility, MNs@Lido was found to possess adequate rigidity to penetrate the cornea without causing any subsequent injury, and the created corneal pinhole channels completely self-healed within 24 h. Interestingly, MNs@Lido exhibited effective analgesic effects for local anesthesia on both heel skin and eyeball, with the sustained anesthetic effect lasting for at least 30 min., Conclusions: These findings indicate that the mosquito proboscis-inspired cambered MNs patch provides rapid and painless local anesthesia, overcoming the limitations of conventional delivery methods of local anesthetics, thus opening up new possibilities in the treatment of ophthalmic diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Production and hosting by Elsevier B.V.)

CoFe@C was first prepared by calcining the precursor of CoFe-metal-organic framework-74 (CoFe-MOF-74), then an electrochemical sensor for the determination of neohesperidin dihydrochalcone (NHDC) was constructed, which was stemmed from the novel CoFe@C/Nafion composite film modified glassy carbon electrode (GCE). The CoFe@C/Nafion composite was verified by field-emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM). Electrochemical impedance spectroscopy (EIS) was used to evaluate its electrical properties as a modified material for an electrochemical sensor. Compared with CoFe-MOF-74 precursor modified electrode, CoFe@C/Nafion electrode exhibited a great synergic catalytic effect and extremely increased the oxidation peak signal of NHDC. The effects of various experimental conditions on the oxidation of NHDC were investigated and the calibration plot was tested. The results bespoken that CoFe@C/Nafion GCE has good reproducibility and anti-interference under the optimal experimental conditions. In addition, the differential pulse current response of NHDC was linear with its concentration within the range 0.08 ~ 20 µmol/L, and the linear regression coefficient was 0.9957. The detection limit was as low as 14.2 nmol/L (S/N = 3). In order to further verify the feasibility of the method, it was successfully used to determine the content of NHDC in Chinese medicine, with a satisfactory result, good in accordance with that of high performance liquid chromatography (HPLC)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Objective: Improved understanding of metabolic obesity phenotypes holds great promise for personalized strategies to combat obesity and its co-morbidities. Such investigation is however lacking in Tibetans with unique living environments and lifestyle in the highlands. Effects of altitude on heterogeneous metabolic obesity phenotypes remain unexplored., Methods: We defined metabolic obesity phenotypes i.e., metabolically healthy/unhealthy and obesity/normal weight in Tibetans (n = 1204) living at 2800 m in the suburb or over 4000 m in pastoral areas. 129 lipoprotein parameters and 25 low-molecular-weight metabolites were quantified and their associations with each phenotype were assessed using logistic regression models adjusting for potential confounders. The metabolic BMI (mBMI) was generated using a machine learning strategy and its relationship with prevalence of obesity co-morbidities and dietary exposures were investigated., Results: Ultrahigh altitude positively associated with the metabolically healthy and non-obese phenotype and had a tendency towards a negative association with metabolically unhealthy phenotype. Phenotype-specific associations were found for 107 metabolites (e.g., lipoprotein subclasses, N-acetyl-glycoproteins, amino acids, fatty acids and lactate, p < 0.05), among which 55 were manipulated by altitude. The mBMI showed consistent yet more pronounced associations with cardiometabolic outcomes than BMI. The ORs for diabetes, prediabetes and hypertriglyceridemia were reduced in individuals residing at ultrahigh altitude compared to those residing at high altitude. The mBMI mediated the negative association between pastoral diet and prevalence of prediabetes, hypertension and hypertriglyceridemia, respectively., Conclusions: We found metabolite markers representing distinct obesity phenotypes associated with obesity co-morbidities and the modification effect of altitude, deciphering mechanisms underlying protective effect of ultrahigh altitude and the pastoral diet on metabolic health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: This study aimed to investigate the selected anatomical factors that can potentially influence temporomandibular joint (TMJ) clicking in young adults by assessing TMJ structures and lateral pterygoid muscle (LPM) function using magnetic resonance imaging (MRI). Methods: The patients were divided into four groups: the healthy control group; the clicking on mouth opening group; the clicking on mouth closing group; and the clicking on mouth opening and closing group. Additionally, we used clinical palpation to evaluate the masticatory muscles' functional state and employed MRI using the OCOR-T1WI-FSE-CLOSED, OSAG-PDW-FSE-CLOSED, and OSAG-PDW-FSE-OPEN sequences to analyze the texture of the lateral pterygoid muscle (LPM). Results: The proportion of any articular disc or condylar morphology class did not differ significantly between the TMJ clicking and HC groups. The articular disc position did not differ significantly between the TMJ clicking and HC groups. In the TMJ clicking group, the presence of masticatory muscle dysfunction differed significantly between the clicking and non-clicking sides. Moreover, the LPM accounted for the highest proportion among masticatory muscles with tenderness in all TMJ clicking subgroups (77.78%-100%). Therefore, in the TMJ clicking group, the LPM texture was less defined, more uniform in gray scale, and more similar to local texture ( p < 0.0001). Conclusion: The occurrence of TMJ clicking in young adults is unrelated to the TMJ structure but related to the function of masticatory muscles, particularly the LPM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Luo, Yang, Yuan, Wang, Qiu, Zhou, Gao, Xu, Yang and Xu.)

Numerous studies have investigated the immunomodulatory effects of yogurt, but the underlying mechanism remained elusive. This study aimed to elucidate the alleviating properties of yogurt on immunosuppression and proposed the underlying mechanism was related to the metabolite D-lactate. In the healthy mice, we validated the safety of daily yogurt consumption (600 μL) or D-lactate (300 mg/kg). In immunosuppressed mice induced by cyclophosphamide (CTX), we evaluated the immune regulation of yogurt and D-lactate. The result showed that yogurt restored body weight, boosted immune organ index, repaired splenic tissue, recovered the severity of delayed-type hypersensitivity reactions and increased serum cytokines (IgA, IgG, IL-6, IFN-γ). Additionally, yogurt enhanced intestinal immune function by restoring the intestinal barrier and upregulating the abundance of Bifidobacterium and Lactobacillus. Further studies showed that D-lactate alleviated immunosuppression in mice mainly by promoting cellular immunity. D-lactate recovered body weight and organ development, elevated serum cytokines (IgA, IgG, IL-6, IFN-γ), enhanced splenic lymphocyte proliferation and increased the mRNA level of T-bet in splenic lymphocyte to bolster Th1 differentiation. Finally, CTX is a chemotherapeutic drug, thus, the application of yogurt and D-lactate in the tumor-bearing mouse model was initially explored. The results showed that both yogurt (600 μL) and D-lactate (300 mg/kg) reduced cyclophosphamide-induced immunosuppression without promoting tumor growth. Overall, this study evaluated the safety, immune efficacy and applicability of yogurt and D-lactate in regulating immunosuppression. It emphasized the potential of yogurt as a functional food for immune regulation, with D-lactate playing a crucial role in its immunomodulatory effects.

Background and Purpose: Defective insulin signalling and dysfunction of the endoplasmic reticulum (ER), driven by excessive lipid accumulation in the liver, is a characteristic feature in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Thromboxane A 2 (TXA 2 ), an arachidonic acid metabolite, is significantly elevated in obesity and plays a crucial role in hepatic gluconeogenesis and adipose tissue macrophage polarization. However, the role of liver TXA 2 /TP receptors in insulin resistance and lipid metabolism is largely unknown., Experimental Approach: TP receptor knockout (TP -/- ) mice were generated and fed a high-fat diet for 16 weeks. Insulin sensitivity, ER stress responses and hepatic lipid accumulation were assessed. Furthermore, we used primary hepatocytes to dissect the mechanisms by which the TXA 2 /TP receptor axis regulates insulin signalling and hepatocyte lipogenesis., Key Results: TXA 2 was increased in diet-induced obese mice, and depletion of TP receptors in adult mice improved systemic insulin resistance and hepatic steatosis. Mechanistically, we found that the TXA 2 /TP receptor axis disrupts insulin signalling by activating the Ca 2+ /calcium calmodulin-dependent kinase II γ (CaMKIIγ)-protein kinase RNA-like endoplasmic reticulum kinase (PERK)-C/EBP homologous protein (Chop)-tribbles-like protein 3 (TRB3) axis in hepatocytes. In addition, our results revealed that the TXA 2 /TP receptor axis directly promoted lipogenesis in primary hepatocytes and contributed to Kupffer cell inflammation., Conclusions and Implications: The TXA 2 /TP receptor axis facilitates insulin resistance through Ca 2+ /CaMKIIγ to activate PERK-Chop-TRB3 signalling. Inhibition of hepatocyte TP receptors improved hepatic steatosis and inflammation. The TP receptor is a new therapeutic target for NAFLD and metabolic syndrome., (© 2023 British Pharmacological Society.)

Patched 1 (PTCH1) is the primary receptor for the sonic hedgehog (SHH) ligand and negatively regulates SHH signalling, an essential pathway in human embryogenesis. Loss-of-function mutations in PTCH1 are associated with altered neuronal development and the malignant brain tumour medulloblastoma. As a result of differences between murine and human development, molecular and cellular perturbations that arise from human PTCH1 mutations remain poorly understood. Here, we used cerebellar organoids differentiated from human induced pluripotent stem cells combined with CRISPR/Cas9 gene editing to investigate the earliest molecular and cellular consequences of PTCH1 mutations on human cerebellar development. Our findings demonstrate that developmental mechanisms in cerebellar organoids reflect in vivo processes of regionalisation and SHH signalling, and offer new insights into early pathophysiological events of medulloblastoma tumorigenesis without the use of animal models., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Qingpi, a well-known traditional Chinese medicine for qi-regulating and commonly processed into three types of pieces, has been widely used in the clinical application of liver disease for thousands of years. In this study, an ultra-high-performance liquid chromatography-quadrupole-time of flight-mass spectrometry approach along with multivariate statistical analysis was developed to assess and characterize the differentiations of three processed products and confirm the potential quality markers of Qingpi. In addition, a systematic analysis combined with network pharmacology and molecular docking was performed to clarify the potential mechanism of Qingpi for the treatment of liver disease. As a result, 18 components were identified and an integrated network of Qingpi-Components-Target-Pathway-Liver Disease was constructed. Eight compounds were finally screened out as the potential quality markers acting on ten main targets and pathways of liver disease. Molecular docking analysis results indicated that the quality markers had a good binding activity with the targets. Overall, this work preliminarily identified the potential quality markers of three processed products of Qingpi, and predicted its targets in the prevention and treatment of liver disease, which can provide supporting information for further study of the pharmacodynamic substances and mechanisms of Qingpi., (© 2023 Wiley-VCH GmbH.)

Importance: Leptospirosis, caused by the spirochete bacteria Leptospira , is a zoonotic disease of humans and animals, accounting for over 1 million annual human cases and over 60,000 deaths. We have characterized operon transcriptional units, identified novel RNA coding regions, and reported evidence of potential posttranscriptional polyadenylation in the Leptospira transcriptomes for the first time using Oxford Nanopore Technology RNA sequencing protocols. The newly identified RNA coding regions and operon transcriptional units were detected only in the pathogenic Leptospira transcriptomes, suggesting their significance in virulence-related functions. This article integrates bioinformatics, infectious diseases, microbiology, molecular biology, veterinary sciences, and public health. Given the current knowledge gap in the regulation of leptospiral pathogenicity, our findings offer valuable insights to researchers studying leptospiral pathogenicity and provide both a basis and a tool for researchers focusing on prokaryotic molecular studies for the understanding of RNA compositions and prokaryotic polyadenylation for their organisms of interest., Competing Interests: The authors declare no conflict of interest.

Shotgun metagenomic sequencing analysis is widely used for microbial profiling of biological specimens and pathogen detection. However, very little is known about the technical biases caused by the choice of analysis software and databases on the biological specimen. In this study, we evaluated different direct read shotgun metagenomics taxonomic profiling software to characterize the microbial compositions of simulated mice gut microbiome samples and of biological samples collected from wild rodents across multiple taxonomic levels. Using ten of the most widely used metagenomics software and four different databases, we demonstrated that obtaining an accurate species-level microbial profile using the current direct read metagenomics profiling software is still a challenging task. We also showed that the discrepancies in results when different databases and software were used could lead to significant variations in the distinct microbial taxa classified, in the characterizations of the microbial communities, and in the differentially abundant taxa identified. Differences in database contents and read profiling algorithms are the main contributors for these discrepancies. The inclusion of host genomes and of genomes of the interested taxa in the databases is important for increasing the accuracy of profiling. Our analysis also showed that software included in this study differed in their ability to detect the presence of Leptospira, a major zoonotic pathogen of one health importance, especially at the species level resolution. We concluded that using different databases and software combinations can result in confounding biological conclusions in microbial profiling. Our study warrants that software and database selection must be based on the purpose of the study., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aberrant arachidonic acid metabolism has been implicated in multiple pathophysiological conditions, and the downstream prostanoids levels are associated with adipocyte dysfunction in obesity. However, the role of thromboxane A 2 (TXA 2 ) in obesity remains unclear. We observed that TXA 2 , through its receptor TP, is a candidate mediator in obesity and metabolic disorders. Obese mice with upregulated TXA 2 biosynthesis (TBXAS1) and TXA 2 receptor (TP) expression in caused insulin resistance and macrophage M1 polarization in white adipose tissue (WAT), which can be prevented by treatment with aspirin. Mechanistically, the activation of TXA 2 -TP signaling axis leads to accumulation of protein kinase Cɛ (PKCɛ), thereby enhancing free fat acid (FFA) induced Toll-like receptor4 (TLR4) proinflammatory macrophage activation and the tumor necrosis factor-a (TNF-a) production in adipose tissues. Importantly, TP knockout mice reduced the accumulation of proinflammatory macrophages and adipocyte hypertrophy in WAT. Thus, our findings demonstrate that TXA 2 -TP axis plays a crucial role in obesity-induced adipose macrophage dysfunction, and rational targeting TXA 2 pathway may improve obesity and its associated metabolic disorders in future. In this work, we establish previously unknown role of TXA 2 -TP axis in WAT. These findings might provide new insight into the molecular pathogenesis of insulin resistance, and indicate rational targeting TXA 2 pathway to improve obesity and its associated metabolic disorders in future., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Excessive hepatic glucose production (HGP) is a major cause of fasting hyperglycemia in diabetes, and antihyperglycemic therapy takes center stage. Nonsteroidal anti-inflammatory drugs, such as acetylsalicylic acid (aspirin), reduce hyperglycemia caused by unrestrained gluconeogenesis in diabetes, but its mechanism is incompletely understood. Here, we reported that aspirin lowers fasting blood glucose and hepatic gluconeogenesis, corresponds with lower thromboxane A2 (TXA2) levels, and the hypoglycemic effect of aspirin could be rescued by TP agonist treatment. On fasting and diabetes stress, the cyclooxygenase (COX)/TXA2/thromboxane A2 receptor (TP) axis was increased in the livers. TP deficiency suppressed starvation-induced hepatic glucose output, thus inhibiting the progression of diabetes, whereas TP activation promoted gluconeogenesis. Aspirin restrains glucagon signaling and gluconeogenic gene expression (phosphoenolpyruvate carboxykinase [PCK1] and glucose-6-phosphatase [G6Pase]) through the TXA2/TP axis. TP mediates hepatic gluconeogenesis by activating PLC/IP3/IP3R signaling, which subsequently enhances CREB phosphorylation via facilitating CRTC2 nuclear translocation. Thus, our findings demonstrate that TXA2/TP plays a crucial role in aspirin's inhibition of hepatic glucose metabolism, and TP may represent a therapeutic target for diabetes., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

An efficient method for visible-light-initiated, nickel-catalyzed Sonogashira C(sp)-C(sp 2 ) coupling has been developed via an energy-transfer mode. Thioxanthen-9-one as a photosensitizer could significantly accelerate the arylation of alkynes with a wide range of (hetero)aryl halides in high yields. The cross-coupling reaction undergoes the stepwise oxidative addition of an arylhalide to nickel(0), transmetalation of the resulting aryl-Ni(II) halide species with Zn(II) acetylide into aryl-Ni(II) acetylide species, energy transfer from the excited state of thioxanthen-9-one to aryl-Ni(II) acetylide, and reductive elimination to the aryl alkyne.