Incorporating body mass index into esophageal manometry metrics and mean nocturnal baseline impedance for the evaluation of gastro-esophageal reflux disease.

This study aims to enhance the effectiveness of high resolution manometry (HRM) and pH-impedance monitoring metrics in distinguishing between gastro-esophageal reflux disease (GERD) and non-GERD. A retrospective propensity score matching (PSM) study was conducted on 643 patients with GERD symptoms. PSM matched 134 GERD patients with 134 non-GERD controls. Body mass index (BMI), intra-esophageal pressure (IEP) and intra-gastric pressure (IGP) were significantly higher in the GERD group compared to the non-GERD group. BMI was correlated with IEP and IGP positively. IGP was positively correlated with esophagogastric (EGJ) pressure (EGJ-P) in participants with EGJ type 1 and 2, but not in participants with EGJ type 3. BMI was correlated with distal MNBI negatively. Logistic regression showed BMI as an independent risk factor for GERD. Receiver operating characteristic curve (ROC) and decision curve analysis (DCA) showed that BMI adjusted EGJ contractile integral (EGJ-CI) and BMI adjusted MNBI were superior to the corresponding original ones in predicting GERD susceptibility. According to the findings, BMI and IGP are the main factors contributing to the development of GERD. BMI affects IEP through the adaptive response of EGJ-P to IGP. Incorporating BMI into the calculations of EGJ-CI and MNBI can improve their ability in predicting GERD susceptibility.

Oral administration of Robinia pseudoacacia L. flower exosome-like nanoparticles attenuates gastric and small intestinal mucosal ferroptosis caused by hypoxia through inhibiting HIF-1α- and HIF-2α-mediated lipid peroxidation.

The prevention and treatment of gastrointestinal mucosal injury caused by a plateau hypoxic environment is a clinical conundrum due to the unclear mechanism of this syndrome; however, oxidative stress and microbiota dysbiosis may be involved. The Robinia pseudoacacia L. flower, homologous to a functional food, exhibits various pharmacological effects, such as antioxidant, antibacterial, and hemostatic activities. An increasing number of studies have revealed that plant exosome-like nanoparticles (PELNs) can improve the intestinal microbiota and exert antioxidant effects. In this study, the oral administration of Robinia pseudoacacia L. flower exosome-like nanoparticles (RFELNs) significantly ameliorated hypoxia-induced gastric and small intestinal mucosal injury in mice by downregulating hypoxia-inducible factor-1α (HIF-1α) and HIF-2α expression and inhibiting hypoxia-mediated ferroptosis. In addition, oral RFELNs partially improved hypoxia-induced microbial and metabolic disorders of the stomach and small intestine. Notably, RFELNs displayed specific targeting to the gastrointestinal tract. In vitro experiments using gastric and small intestinal epithelial cell lines showed that cell death caused by elevated HIF-1α and HIF-2α under 1% O2 mainly occurred via ferroptosis. RFELNs obviously inhibited HIF-1α and HIF-2α expression and downregulated the expression of NOX4 and ALOX5, which drive reactive oxygen species production and lipid peroxidation, respectively, suppressing ferroptosis under hypoxia. In conclusion, our findings underscore the potential of oral RFELNs as novel, naturally derived agents targeting the gastrointestinal tract, providing a promising therapeutic approach for hypoxia-induced gastric and small intestinal mucosal ferroptosis.

Therapeutic potential of plant-derived natural compounds in Alzheimer's disease: Targeting microglia-mediated neuroinflammation.

Microglia are resident immune cells of the central nervous system (CNS) with roles in sensing, housekeeping, and defense. Exploring the role of microglia in the occurrence and development of Alzheimer's disease (AD) and the possible therapeutic mechanism of plant-derived natural compounds (PDNCs) that regulate microglia-associated neuroinflammation may potentially help in elucidating the pathogenesis of AD and provide novel insights for its treatment. This review explores the role of abnormal microglial activation and its dominant neuroinflammatory response, as well as the activation of their target receptors and signaling pathways in AD pathogenesis. Additionally, we report an update on the potential pharmacological mechanisms of multiple PDNCs in modulating microglia-associated neuroinflammation in AD treatment. Dysregulated activation of microglial receptors and their downstream pathways impaired immune homeostasis in animal models of AD. Multiple signaling pathways, such as mitogen-activated protein kinase (MAPK), nuclear factor kappa light chain enhancer of activated B cells (NF-κB), and Toll-like receptors, play important roles in microglial activation and can exacerbate microglia-mediated neuroinflammation. PDNCs, such as magnolol, stigmasterol, matrine, naringenin, naringin, and resveratrol, can delay the progression of AD by inhibiting the proinflammatory receptors of microglia, activating its anti-inflammatory receptors, regulating the receptors related to ß-amyloid (Aß) clearance, reversing immune dysregulation, and maintaining the immune homeostasis of microglial downstream pathways. This review summarizes the mechanisms by which microglia cause chronic inflammation in AD and evaluates the beneficial effects of PDNCs on immune regulation in AD by regulating microglial receptors and their downstream pathways.

Universal Copolymerization of Crosslinked Polyether Electrolytes for All-Solid-State Lithium-Metal Batteries.

Solid polymer electrolytes (SPEs) are pivotal in advancing the practical implementation of all-solid-state batteries. Poly(1,3-dioxane) (PDOL)-based electrolytes have attracted significant attention due to the pseudo-high conductivity achieved through sophisticated in situ polymerization methods; however, such PDOL-based electrolytes present challenges of crystallization over time and monomers residual during processing. In this study, integrating LiTFSI and LiDFOB as a universal copolymerization strategy for developing high-performance PDOL electrolytes with a wide range of epoxy crosslinkers is proposed. It is discovered that this approach leverages the protective effects of TFSI anions on the boron active center and catalyzes polymer chain growth via crosslinking. The homogenously crosslinked (benzene-centered) PDOL electrolyte exhibits remarkable thermo-mechanical stability (up to 100 °C), high ion migration number (tLi+ = 0.42), a wide electrochemical window (≈5.0 V vs Li+/Li), and high ionic conductivity (4.5×10-4 S cm-1). Notably, the crosslinked PDOL electrolyte is in the all-solid-state with minimal monomer/oligomer residual, exhibiting no crystallization during relaxation, delivering a robust performance in all-solid-state lithium metal batteries.

Effects of discharge plasma on seed germination and volatile compounds content of Agropyron Mongolicum.

To investigate the effects of discharge plasma on Agropyron mongolicum seeds, various treatments including direct exposure to discharge plasma, combined treatment with discharge plasma and plasma-activated water (PAW) were applied to the seeds. The changes in germination rate, MDA content, and volatile compound levels of Agropyron mongolicum seeds after different treatments were examined. The results showed that the direct effect of plasma had no significant effect on the MDA content or germination rate of Agropyron mongolicum seeds due to the limited penetration depth. However, the combined effect of plasma and activated water could cause active nitrogen and oxygen particles to enter the seeds and cause oxidative stress damage. After 18 h of combined treatment, the MDA content increased significantly, and the germination rate decreased to below the semilethal dose, which was 33.44 %. After plasma treatment, 55 volatile compounds, mainly alcohols, aldehydes and ketones, were identified from the seeds of Agropyron mongolicum. Due to the oxidation and modification of the plasma, the content of most aldehydes increased with increasing reaction time. After screening, 13 volatile organic compounds could be used as potential markers to distinguish between different treatment methods. These results reveal the mechanism underlying the biological effects of plasma treatment on Agropyron mongolicum seeds.

CaMKII autophosphorylation is the only enzymatic event required for synaptic memory.

Ca2+/calmodulin (CaM)-dependent kinase II (CaMKII) plays a critical role in long-term potentiation (LTP), a well-established model for learning and memory through the enhancement of synaptic transmission. Biochemical studies indicate that CaMKII catalyzes a phosphotransferase (kinase) reaction of both itself (autophosphorylation) and of multiple downstream target proteins. However, whether either type of phosphorylation plays any role in the synaptic enhancing action of CaMKII remains hotly contested. We have designed a series of experiments to define the minimal requirements for the synaptic enhancement by CaMKII. We find that autophosphorylation of T286 and further binding of CaMKII to the GluN2B subunit are required both for initiating LTP and for its maintenance (synaptic memory). Once bound to the NMDA receptor, the synaptic action of CaMKII occurs in the absence of target protein phosphorylation. Thus, autophosphorylation and binding to the GluN2B subunit are the only two requirements for CaMKII in synaptic memory.

A syrup containing L-arabinose and D-xylose appears superior to PEG-4000 as a bowel cleansing agent.

Adequate bowel cleansing is crucial for endoscopic diagnosis and treatment, and the recovery of gut microbiota after intestinal cleansing is also important. A hypertonic syrup predominantly comprising L-arabinose and D-xylose (20% xylo-oligosaccharides) can be extracted from the hemicellulose of corn husks and cobs. L-Arabinose and xylo-oligosaccharides have been reported to relieve constipation and improve the gut microbial environment. This study evaluated the bowel cleansing effect of the aforementioned syrup and its influence on the organism and intestinal microbiota after cleansing in comparison with polyethylene glycol-4000 (PEG-4000) in mice. Bowel cleansing was performed using syrup or PEG-4000 in C57BL/6J mice, and the effect of intestinal preparation and its influence on serum electrolytes and gut microbiota after bowel cleansing were evaluated. The volume of intestinal residual feces in the syrup group was significantly lower than that in the PEG-4000 group. Additionally, syrup disturbed serum electrolytes more mildly than PEG-4000. Alpha diversity in the gut microbiota was significantly higher in the syrup group than in the PEG-4000 group on the first day after bowel cleansing. However, no difference in beta diversity was observed between the two groups. Syrup increased the abundance of Bifidobacteria and Christensenella and decreased the abundance of Akkermansia in comparison with PEG-4000 on the first day after bowel cleansing. Thus, this syrup has potential clinical use as a bowel cleansing agent given the above effects, its benefits and safety, and better taste and acceptability.

Vitamin D receptor gene polymorphisms, bioavailable 25-hydroxyvitamin D, and hepatocellular carcinoma survival.

BACKGROUND: Little is known about the role of vitamin D receptor polymorphisms and their interaction with vitamin D status in hepatocellular carcinoma (HCC) prognosis. METHODS: We evaluated the association of TaqI, BsmI, Cdx-2, and ApaI polymorphisms, individually and in combination, with liver cancer-specific (LCSS) and overall survival (OS) among 967 patients with newly diagnosed HCC. Subsequently, we examined whether these polymorphisms modified the association between serum bioavailable 25-hydroxyvitamin D (25OHD) concentrations and survival. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 1017 days, 393 deaths occurred, with 360 attributed to HCC. Having TaqI G allele (HRper allele = 1.30, 95% CI = 1.08 to 1.57) or BsmI T allele (HRper allele = 1.41, 95% CI = 1.01 to 1.99) was associated with worse LCSS. Carrying increasing numbers of protective alleles was associated with superior LCSS (HR6-8 vs 0-3 = 0.52, 95% CI = 0.34 to 0.80). The inverse association of bioavailable 25OHD with LCSS was only significant in patients with TaqI AA (HRQuartile 4 vs Quartile 1 = 0.63, 95% CI = 0.44 to 0.92), BsmI CC (HRQuartile 4 vs Quartile 1 = 0.62, 95% CI = 0.44 to 0.88), and 6 to 8 protective alleles (HRQuartile 4 vs Quartile 1 = 0.45, 95% CI = 0.23 to 0.87). Similar associations were observed for OS. CONCLUSIONS: Patients carrying wild-type TaqI, BsmI, or more protective alleles had improved survival and might benefit from optimizing bioavailable 25OHD status.

Distinct profiles of cerebral oxygenation in focal vs. secondarily generalized EEG seizures in children undergoing cardiac surgery.

Objectives: Seizures are common in children undergoing cardiopulmonary bypass (CPB). Cerebral oxygen saturation (ScO2) by near-infrared spectroscopy is routinely monitored in many centers, but the relations between the levels and changes of ScO2 and brain injuries remain incompletely understood. We aimed to analyze the postoperative profiles of ScO2 and cerebral blood flow velocity in different types of EEG seizures in relation to brain injuries on MRI. Methods: We monitored continuous EEG and ScO2 in 337 children during the first 48 h after CPB, which were analyzed in 3 h periods. Cerebral blood flow peak systolic velocity (PSV) in the middle cerebral artery was measured daily by transcranial Doppler. Postoperative cerebral MRI was performed before hospital discharge. Results: Based on the occurrence and spreading types of seizures, patients were divided into three groups as patients without seizures (Group N; n = 309), those with focal seizures (Group F; n = 13), or with secondarily generalized seizures (Group G; n = 15). There were no significant differences in the onset time and duration of seizures and incidence of status epilepticus between the two seizures groups (Ps ≥ 0.27). ScO2 increased significantly faster across Group N, Group G, and Group F during the 48 h (p < 0.0001) but its overall levels were not significantly different among the three groups (p = 0.30). PSV was significantly lower (p = 0.003) but increased significantly faster (p = 0.0003) across Group N, Group G, and Group F. Group F had the most severe brain injuries and the highest incidence of white matter injuries on MRI among the three groups (Ps ≤ 0.002). Conclusion: Postoperative cerebral oxygenation showed distinct profiles in secondarily generalized and particularly focal types of EEG seizures in children after CPB. A state of 'overshooting' ScO2 with persistently low PSV was more frequently seen in those with focal seizures and more severe brain injury. Information from this study may have important clinical implications in detecting brain injuries when monitoring cerebral oxygenation in this vulnerable group of children after CPB.

Dual-phase nano-glass-hydrides overcome the strength-ductility trade-off and magnetocaloric bottlenecks of rare earth based amorphous alloys.

Metal-hydrogen systems have attracted intense interest for diverse energy-related applications. However, metals usually reduce their ductility after hydrogenation. Here, we show that hydrogen can take the form of nano-sized ordered hydrides (NOH) homogeneously dispersed in a stable glassy shell, leading to remarkable enhancement in both strength and ductility. The yield strength is enhanced by 44% and the plastic strain is substantially improved from almost zero to over 70%, which is attributed to the created NOH and their interplay with the glassy shell. Moreover, the hydride-glass composite GdCoAlH possesses a giant magnetic entropy change (-ΔSM) of 18.7 J kg-1K-1 under a field change of 5 T, which is 105.5% larger than the hydrogen-free sample and is the largest value among amorphous alloys and related composites. The prominent ΔSM-ductility combination overcomes the bottlenecks of amorphous alloys as magnetic refrigerants. These results provide a promising strategy for property breakthrough of structural-functional alloys.

AIDA-1/ANKS1B Binds to the SynGAP Family RasGAPs with High Affinity and Specificity.

AIDA-1, encoded by ANKS1B, is an abundant postsynaptic scaffold protein essential for brain development. Mutations of ANKS1B are closely associated with various psychiatric disorders. However, very little is known regarding the molecular mechanisms underlying AIDA-1's involvements under physiological and pathophysiological conditions. Here, we discovered an interaction between AIDA-1 and the SynGAP family Ras-GTPase activating protein (GAP) via affinity purification using AIDA-1d as the bait. Biochemical studies showed that the PTB domain of AIDA-1 binds to an extended NPx[F/Y]-motif of the SynGAP family proteins with high affinities. The high-resolution crystal structure of AIDA-1 PTB domain in complex with the SynGAP NPxF-motif revealed the molecular mechanism governing the specific interaction between AIDA-1 and SynGAP. Our study not only explains why patients with ANKS1B or SYNGAP1 mutations share overlapping clinical phenotypes, but also allows identification of new AIDA-1 binding targets such as Ras and Rab interactors.

Demixing is a default process for biological condensates formed via phase separation.

Excitatory and inhibitory synapses do not overlap even when formed on one submicron-sized dendritic protrusion. How excitatory and inhibitory postsynaptic cytomatrices or densities (e/iPSDs) are segregated is not understood. Broadly, why membraneless organelles are naturally segregated in cellular subcompartments is unclear. Using biochemical reconstitutions in vitro and in cells, we demonstrate that ePSDs and iPSDs spontaneously segregate into distinct condensed molecular assemblies through phase separation. Tagging iPSD scaffold gephyrin with a PSD-95 intrabody (dissociation constant ~4 nM) leads to mistargeting of gephyrin to ePSD condensates. Unexpectedly, formation of iPSD condensates forces the intrabody-tagged gephyrin out of ePSD condensates. Thus, instead of diffusion-governed spontaneous mixing, demixing is a default process for biomolecules in condensates. Phase separation can generate biomolecular compartmentalization specificities that cannot occur in dilute solutions.

Therapeutic Applications of Nanomedicine: Recent Developments and Future Perspectives.

The concept of nanomedicine has evolved significantly in recent decades, leveraging the unique phenomenon known as the enhanced permeability and retention (EPR) effect. This has facilitated major advancements in targeted drug delivery, imaging, and individualized therapy through the integration of nanotechnology principles into medicine. Numerous nanomedicines have been developed and applied for disease treatment, with a particular focus on cancer therapy. Recently, nanomedicine has been utilized in various advanced fields, including diagnosis, vaccines, immunotherapy, gene delivery, and tissue engineering. Multifunctional nanomedicines facilitate concurrent medication delivery, therapeutic monitoring, and imaging, allowing for immediate responses and personalized treatment plans. This review concerns the major advancement of nanomaterials and their potential applications in the biological and medical fields. Along with this, we also mention the various clinical translations of nanomedicine and the major challenges that nanomedicine is currently facing to overcome the clinical translation barrier.

Association between Body Mass Index and Medication-Overuse Headache among Individuals with Migraine: A Cross-Sectional Study.

INTRODUCTION: Medication-overuse headache (MOH) is a secondary chronic headache disorder that occurs in individuals with a pre-existing primary headache disorder, particularly migraine disorder. Obesity is often combined with chronic daily headaches and is considered a risk factor for the transformation of episodic headaches into chronic headaches. However, the association between obesity and MOH among individuals with migraine has rarely been studied. The present study explored the association between body mass index (BMI) and MOH in people living with migraine. METHODS: This cross-sectional study is a secondary analysis of data from the Survey of Fibromyalgia Comorbidity with Headache study. Migraine and MOH were diagnosed using the criteria of the International Classification of Headache Disorders, 3rd Edition. BMI (kg/m2) is calculated by dividing the weight (kg) by the square of the height (m). Multivariable logistic regression analysis was used to evaluate the association between BMI and MOH. RESULTS: A total of 2,251 individuals with migraine were included, of whom 8.7% (195/2,251) had a concomitant MOH. Multivariable logistic regression analysis, adjusted for age, sex, education level, headache duration, pain intensity, headache family history, chronic migraine, depression, anxiety, insomnia, and fibromyalgia, demonstrated there was an association between BMI (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01-1.11; p = 0.031) and MOH. The results remained when the BMI was transformed into a category. Compared to individuals with Q2 (18.5 kg/m2 ≤ BMI ≤23.9 kg/m2), those with Q4 (BMI ≥28 kg/m2) had an adjusted OR for MOH of 1.81 (95% CI, 1.04-3.17; p = 0.037). In the subgroup analyses, BMI was associated with MOH among aged more than 50 years (OR, 1.13; 95%, 1.03-1.24), less than high school (OR, 1.08; 95%, 1.01-1.15), without depression (OR, 1.06; 95%, 1.01-1.12), and without anxiety (OR, 1.06; 95%, 1.01-1.12). An association between BMI and MOH was found in a sensitivity analysis that BMI was classified into four categories according to the World Health Organization guidelines. CONCLUSION: In this cross-sectional study, BMI was associated with MOH in Chinese individuals with migraine.

Artificial Intelligence-Driven Platform: Unveiling Critical Hepatic Molecular Alterations in Hepatocellular Carcinoma Development.

Since most Hepatocellular Carcinoma (HCC) typically arises as a consequence of long-term liver damage, the hepatic molecular characteristics are closely related to the occurrence of HCC. Gaining comprehensive information about the location, morphology, and hepatic molecular alterations related to HCC is essential for accurate diagnosis. However, there is a dearth of technological advancements capable of concurrently providing precise HCC diagnosis and discerning the accompanying hepatic molecular alterations. In this study, an integrated information system is developed for the pathological-level diagnosis of HCC and the revelation of critical molecular alterations in the liver. This system utilizes computed tomography/Surface-enhanced Raman scattering combined with an artificial intelligence strategy to establish connections between the occurrence of HCC and alterations in hepatic biomolecules. Employing artificial intelligence techniques, the SERS spectra from both healthy and HCC groups are successfully classified into two distinct categories with a remarkable accuracy rate of 91.38%. Based on molecular profiling, it is identified that the nucleotide-to-lipid signal ratio holds significant potential as a reliable indicator for the occurrence of HCC, thereby serving as a promising tool for prevention and therapeutic surveillance.

Geochemical Characteristics of Trace Elements and Mineralization Model of the Ediacaran-Early Cambrian Phosphorites, South China.

As a nonrenewable resource, phosphate rock is an important support for the development and survival of the national economy. The regional distribution and output of phosphate rock in China are extremely uneven, and the amount of high-quality ore resources is relatively poor, which seriously restricts the development and utilization of phosphate rock resources in China. This paper briefly summarizes the distribution characteristics of phosphate rock resources and summarizes the characteristics and research progress of Ediacaran-early Cambrian phosphorus mineralization types, geological characteristics, and deposit genesis of the Yangtze platform in South China. The Ediacaran-early Cambrian sedimentary phosphorite deposits in China are mainly distributed in Yunnan, Guizhou, Hubei, Sichuan and Hunan provinces of the Yangtze platform, in which the early Cambrian phosphate deposits are also rich in rare earth elements, associated with uranium, nickel, molybdenum, vanadium, and other beneficial metal elements. The increase of atmospheric oxygen content at the Ediacaran-Cambrian boundary may have promoted the extensive oxygenation of the late Neoproterozoic oceans, so the Ediacaran-early Cambrian oceans generally showed a reductive environment, and there may be dynamic chemical stratification of the oxidation zone-sulfide zone-iron zone. Up to the early Cambrian, the redox stratified structure of Precambrian seawater may still be inherited, showing that the surface water is an oxidizing environment, changing to a reduction environment, and even wedge-shaped sulfide water is developed at the bottom of the deep basin. The main phosphorus sources are deep phosphorus-rich seawater, continental weathering, and deep hydrothermal activity of Ediacaran-early Cambrian marine sedimentary phosphorite deposits in South China. The genetic mechanisms of phosphorite deposits in the Yangtze platform in South China are mainly biogenic, upwelling phosphorus-forming theory, mechanical mineralization, and syn-sedimentary hot water mixed genesis. In the future, it is still necessary to further explore the internal relationship between phosphorus deposits and major geological events, the in situ analysis of microstructure of phosphate rock ores, and the genetic mechanism of phosphate deposits and the reconstruction of paleo-marine environment.

Rimegepant orally disintegrating tablet 75 mg for acute treatment of migraine in adults from China: a subgroup analysis of a double-blind, randomized, placebo-controlled, phase 3 clinical trial.

BACKGROUND: Rimegepant orally disintegrating tablet (ODT), an oral small-molecule calcitonin gene-related peptide receptor antagonist, is indicated for acute and preventive treatment of migraine in the United States and other countries. Previously, a large clinical trial assessed the efficacy and safety of rimegepant ODT 75 mg for the acute treatment of migraine in adults living in China or South Korea. A post hoc subgroup analysis of this trial was performed to evaluate the efficacy and safety of rimegepant for acute treatment of migraine in adults living in China. METHODS: Eligible participants were ≥ 18 years of age and had a ≥ 1-year history of migraine, with 2 to 8 attacks of moderate or severe pain intensity per month and < 15 headache days per month during the 3 months before screening. Participants self-administered rimegepant ODT 75 mg or matching placebo to treat a single migraine attack of moderate or severe pain intensity. The co-primary endpoints were pain freedom and freedom from the most bothersome symptom (MBS) at 2 h post-dose. Key secondary endpoints included pain relief at 2 h post-dose, ability to function normally at 2 h post-dose, use of rescue medication within 24 h post-dose, and sustained pain freedom from 2 to 24 h and 2 to 48 h post-dose. All p values were nominal. Safety was assessed via treatment-emergent adverse events (TEAEs), electrocardiograms, vital signs, and routine laboratory tests. RESULTS: Overall, 1075 participants (rimegepant, n = 538; placebo, n = 537) were included in the subgroup analysis. Rimegepant was more effective than placebo for the co-primary endpoints of pain freedom (18.2% vs. 10.6%, p = 0.0004) and freedom from the MBS (48.0% vs. 31.8%, p <  0.0001), as well as all key secondary endpoints. The incidence of TEAEs was comparable between the rimegepant (15.2%) and placebo (16.4%) groups. No signal of drug-induced liver injury was observed, and no study drug-related serious TEAEs were reported in the rimegepant group. CONCLUSIONS: A single dose of rimegepant 75 mg rimegepant was effective for the acute treatment of migraine in adults living in China, with safety and tolerability similar to placebo. TRIAL REGISTRATION: Clinicaltrials.gov NCT04574362 Date registered: 2020-10-05.

Simulation of Dispersion and Explosion Characteristics of LiFePO4 Lithium-Ion Battery Thermal Runaway Gases.

In recent years, as the installed scale of battery energy storage systems (BESS) continues to expand, energy storage system safety incidents have been a fast-growing trend, sparking widespread concern from all walks of life. During the thermal runaway (TR) process of lithium-ion batteries, a large amount of combustible gas is released. In this paper, the 105 Ah lithium iron phosphate battery TR test was conducted, and the flammable gas components released from the battery TR were detected. The simulation tests of the diffusion and explosion characteristics of lithium iron phosphate battery's (LFP) TR gases with different numbers and positions in the BESS were carried out using FLACS simulation software. It was found that the more batteries TR simultaneously, the shorter the time for the combustible gas concentration in the energy storage cabin to reach the explosion limit. When 48 batteries were in TR simultaneously in the energy storage cabin, the shortest time was 9.8 s, and the further the location of the fire is from the hatch, the largest explosion overpressure is generated to the hatch, up to 583 kPa. When the gas generated by the TR of 48 batteries explodes, the maximum explosion overpressure at 5 m outside the energy storage cabin hatch is more significant than 40 kPa, which will cause serious injury to humans. The causes of TR of batteries in prefabricated chambers are complex, and the location and amount of thermal runaway of batteries as well as the diffusion of combustible fumes can have different effects on the external environment. The research results can provide support for the safety design of BESS.

Short-distance vesicle transport via phase separation.

In addition to long-distance molecular motor-mediated transport, cellular vesicles also need to be moved at short distances with defined directions to meet functional needs in subcellular compartments but with unknown mechanisms. Such short-distance vesicle transport does not involve molecular motors. Here, we demonstrate, using synaptic vesicle (SV) transport as a paradigm, that phase separation of synaptic proteins with vesicles can facilitate regulated, directional vesicle transport between different presynaptic bouton sub-compartments. Specifically, a large coiled-coil scaffold protein Piccolo, in response to Ca2+ and via its C2A domain-mediated Ca2+ sensing, can extract SVs from the synapsin-clustered reserve pool condensate and deposit the extracted SVs onto the surface of the active zone protein condensate. We further show that the Trk-fused gene, TFG, also participates in COPII vesicle trafficking from ER to the ER-Golgi intermediate compartment via phase separation. Thus, phase separation may play a general role in short-distance, directional vesicle transport in cells.