In Situ Constructed Spinel Layer Stabilized Upcycled LiCoO2 for High Performance Lithium-Ion Batteries.

With ever-increasing requirements for cathodes in the lithium-ion batteries market, an efficiency and eco-friendly upcycling regeneration strategy is imperative to meet the demand for high-performance cathode materials. Herein, a facile, direct and upcycling regeneration strategy is proposed to restore the failed LiCoO2 and enhance the stability at 4.6 V. Double effects combination of relithiation and outside surface reconstruction are simultaneously achieved via a facile solid-phase sintering method. The evolution process of the Li-supplement and grain-recrystallization is systematically investigated, and the high performance of the upcycled materials at high voltage is comprehensively demonstrated. Thanks to the favorable spinel LiCoxMn2-xO4 surface coating, the upcycled sample displays outstanding electrochemical performance, superior to the pristine cathode materials. Notably, the 1% surface-coated LiCoO2 achieves a high discharge-specific capacity of 207.9 mA h g-1 at 0.1 C and delivers excellent cyclability with 77.0% capacity retention after 300 cycles. Significantly, this in situ created spinel coating layer can be potentially utilized for recycling spent LiCoO2, thus providing a viable, promising recycling strategy insights into the upcycling of degraded cathodes.

Fluorinated Surface Engineering towards High-rate and Durable Potassium-ion Battery.

Solid electrolyte interphase (SEI) crucially affects the rate performance and cycling lifespan, yet to date more extensive research is still needed in potassium-ion batteries. We report an ultra-thin and KF-enriched SEI triggered by tuned fluorinated surface design in electrode. Our results reveal that fluorination engineering alters the interfacial chemical environment to facilitate inherited electronic conductivity, enhance adsorption ability of potassium, induce localized surface polarization to guide electrolyte decomposition behavior for SEI formation, and especially, enrich the KF crystals in SEI by self-sacrifice from C-F bond cleavage. Hence, the regulated fluorinated electrode with generated ultra-thin, uniform, and KF-enriched SEI shows improved capacity of 439.3 mAh g-1 (3.82 mAh cm--2), boosted rate performance (202.3 mAh g-1 at 8.70 mA cm-2) and durable cycling performance (even under high loading of ~8.7 mg cm-2). We expect this practical engineering principle to open up new opportunities for upgrading the development of potassium-ion batteries.

Vanadium Metal Doping of Monolayer MoS2 for p-Type Transistors and Fast-Speed Phototransistors.

Modulating the electrical properties of two-dimensional (2D) materials is a fundamental prerequisite for their development to advanced electronic and optoelectronic devices. Substitutional doping has been demonstrated as an effective method for tuning the band structure in monolayer 2D materials. Here, we demonstrate a facile selective-area growth of vanadium-doped molybdenum disulfide (V-doped MoS2) flakes via pre-patterned vanadium-metal-assisted chemical vapor deposition (CVD). Optical microscopy characterization revealed the presence of flake arrays. Transmission electron microscopy, Raman spectroscopy, and X-ray photoelectron spectroscopy were employed to identify the chemical composition and crystalline structure of as-grown flakes. Electrical measurements indicated a light p-type conduction behavior in monolayer V-doped MoS2. Furthermore, the response time of phototransistors based on V-doped MoS2 monolayers exhibited a remarkable capability of 3 ms, representing approximately 3 orders of magnitude faster response than that observed in pure MoS2 phototransistors. This work hereby provides a feasible approach to doping of 2D materials, promising a scalable pathway for the integration of these materials into emerging electronic and optoelectronic devices.

Development of Detection Antibody Targeting the Linear Epitope in SARS-CoV-2 Nucleocapsid Protein with Ultra-High Sensitivity.

The COVID-19 pandemic caused by SARS-CoV-2 highlighted the importance of reliable detection methods for disease control and surveillance. Optimizing detection antibodies by rational screening antigens would improve the sensitivity and specificity of antibody-based detection methods such as colloidal gold immunochromatography. In this study, we screened three peptide antigens with conserved sequences in the N protein of SARS-CoV-2 using bioinformatical and structural biological analyses. Antibodies that specifically recognize these peptides were prepared. The epitope of the peptide that had the highest binding affinity with its antibody was located on the surface of the N protein, which was favorable for antibody binding. Using the optimal antibody that can recognize this epitope, we developed colloidal gold immunochromatography, which can detect the N protein at 10 pg/mL. Importantly, this antibody could effectively recognize both the natural peptide antigen and mutated peptide antigen in the N protein, showing the feasibility of being applied in the large-scale population testing of SARS-CoV-2. Our study provides a platform with reference significance for the rational screening of detection antibodies with high sensitivity, specificity, and reliability for SARS-CoV-2 and other pathogens.

Recent Advances and Opportunities in Reactivating Inactive Lithium in Batteries.

The loss of active materials is one of the main culprits of the battery failures. As a typical example, the presence of inactive lithium, also known as "dead lithium", contributes to the rapid capacity deterioration and reduces energy output in lithium batteries. This phenomenon has long been recognized as irreversible. In this Minireview, the first of this kind, we aim to summarize the formation of inactive lithium and reassess its impact on battery performance metrics. Additionally, we explore various strategies that have been devised to rejuvenate inactive lithium. This comprehensive overview of the latest advancements in reactivating inactive lithium not only offers insights into restoring capacity and enhancing battery performance metrics but also provides a foundation for future research in reviving other inactive materials found in next-generation batteries, such as lithium metal batteries, lithium-sulfur batteries, other alkali metal batteries, and liquid flow batteries.

Contralateral Neck-shaft Angle Lower Than 130° Is Associated With Clinical Failure in Nongeriatric Individuals: Analysis of the National Femoral Neck Fracture Database of 1066 Patients.

BACKGROUND: Treatment of femoral neck fractures in patients who are nongeriatric (≤ 60 years) is challenging because of high failure rates. Anatomic parameters influence the biomechanical environment for fracture healing, but their associations with clinical prognosis remains unclear. QUESTIONS/PURPOSES: (1) Which anatomic parameter that is identifiable on pelvic radiographs shows a statistical correlation with a higher risk of clinical failure defined as nonunion, avascular necrosis (AVN), reoperation, and functional failure (decrease in Harris hip score reaching the minimum clinically important difference) in the screw fixation of femoral neck fractures among nongeriatric patients? (2) How does the influence of anatomic parameters on clinical prognosis manifest: directly or mediated by additional mechanisms? METHODS: This retrospective, multicenter study used a nationwide database in China. Between January 2014 and December 2020, we evaluated 1066 patients with femoral neck fractures with a median age of 53 years (interquartile range 46 to 56) and median follow-up period of 62 months. Anatomic parameters including femoral neck-shaft angle (NSA), femoral head radius, femoral neck width, femoral offset, acetabular center-edge angle, and acetabular sharp angle were variables of interest. The primary outcome was clinical failure including nonunion, AVN, reoperation, and functional failure (decrease in Harris hip score reaching the minimum clinically important difference). Risk factors for failure were first filtered using the Bayesian information criterion and then assessed with multiple regression adjusting for confounders. The mediation effect was further explored using model-based causal mediation analysis with a quasi-Bayesian Monte Carlo method. RESULTS: Of all anatomic parameters we assessed, the contralateral NSA was associated with clinical failure, after adjusting for all potential covariates and confounding variables (adjusted odds ratio 0.92 [95% confidence interval 0.89 to 0.95]; p < 0.001). The optimal threshold for the NSA was 130°, with the highest Youden index of 0.27. Patients with an NSA < 130° (41% [441 of 1066]) demonstrated an increased occurrence of nonunion (15% [68 of 441] versus 5% [33 of 625]; p < 0.001), AVN (32% [141 of 441] versus 22% [136 of 625]; p < 0.001), functional failure (25% [110 of 441] versus 15% [93 of 625]), and reoperations (28% [122 of 441] versus 13% [79 of 625]). The impact of an NSA less than 130° on clinical failure was direct and substantially mediated by the type of displaced fracture (mediation proportion: 18.7%). CONCLUSION: In our study of screw fixations for femoral neck fractures among nongeriatric patients, we identified that a contralateral NSA < 130° correlates with an increased risk of clinical failure including nonunion, AVN, functional failure, and reoperation. The effect is either direct or mediated through displaced fracture types. This is important for surgeons in order to recognize the elevated rate of clinical failure and nature of the challenging biomechanical environment, which should guide them in refining surgical details and selecting appropriate fixation and rehabilitation plans. Approaches to managing these fractures require further validation with large-scale clinical trials. LEVEL OF EVIDENCE: Level III, prognostic study.

Identification of Eukaryotic Translation Initiation Factor 4B as a Novel Candidate Gene for Congenital Hypothyroidism.

CONTEXT: Congenital hypothyroidism (CH) is the most common endocrine disorder in neonates, but its etiology is still poorly understood. OBJECTIVE: We performed whole exome sequencing to identify novel causative gene for CH and functional studies to validate its role in the occurrence of CH. METHODS: Whole exome sequencing in 98 CH patients not harboring known CH candidate genes and bioinformatic analysis were performed. Functional analysis was performed using morpholino, a synthetic short antisense oligonucleotide that contains 25 DNA bases on a methylene morpholine backbone, in zebrafish and CRISPR‒Cas9-mediated gene knockout in mice. RESULTS: Eukaryotic translation initiation factor 4B (EIF4B) was identified as the most promising candidate gene. The EIF4B gene was inherited in an autosomal recessive model, and one patient with thyroid dysgenesis carried EIF4B biallelic variants (p.S430F/p.P328L). In zebrafish, the knockdown of eif4ba/b expression caused thyroid dysgenesis and growth retardation. Thyroid hormone levels were significantly decreased in morphants compared with controls. Thyroxine treatment in morphants partially rescued growth retardation. In mice, the homozygous conceptuses of Eif4b+/- parents did not survive. Eif4b knockout embryos showed severe growth retardation, including thyroid dysgenesis and embryonic lethality before E18.5. CONCLUSION: These experimental data supported a role for EIF4B function in the pathogenesis of the hypothyroid phenotype seen in CH patients. Our work indicated that EIF4B was identified as a novel candidate gene in CH. EIF4B is essential for animal survival, but further studies are needed to validate its role in the pathogenesis of CH.

Dual-specificity tyrosine phosphorylation-regulated kinase 1A promotes the inclusion of amyloid precursor protein exon 7.

Extracellular amyloid plaques made of Amyloid-ß (Aß) derived from amyloid precursor protein (APP) is one of the major neuropathological hallmarks of Alzheimer's disease (AD). There are three major isoforms of APP, APP770, APP751, and APP695 generated by alternative splicing of exons 7 and 8. Exon 7 encodes the Kunitz protease inhibitor (KPI) domain. Its inclusion generates APP isoforms containing KPI, APPKPI+, which is elevated in AD and Down syndrome (DS) brains and associated with increased Aß deposition. Dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) phosphorylates many splicing factors and regulates the alternative splicing of pre-mRNA. It is upregulated in DS and AD brain. However, it is not yet clear whether Dyrk1A could regulate APP alternative splicing. In the present study, we overexpressed or knocked down Dyrk1A in cultured cells and observed that Dyrk1A promoted the inclusion of both APP exons 7 and 8. Moreover, a significant increase in APP exon7 inclusion was also detected in the forebrain and hippocampus of human Dyrk1A transgenic mice - Tg/Dyrk1A. Screening for splicing factors regulated by Dyrk1A revealed that serine/arginine-rich protein 9G8 inhibited APP exon7 inclusion and interacted with APP pre-mRNA. In vitro, expression of exon 7 facilitated APP cleavage. In human Dyrk1A transgenic mice, we also found an increase in Aß production. These findings suggest that Dyrk1A inhibits the splicing factor 9G8 and promotes APP exon 7 inclusion, leading to more APPKPI+ expression and APP cleavage and potentially contributing to Aß production in vivo.

Deficiency of the HGF/Met pathway leads to thyroid dysgenesis by impeding late thyroid expansion.

The mechanisms of bifurcation, a key step in thyroid development, are largely unknown. Here we find three zebrafish lines from a forward genetic screening with similar thyroid dysgenesis phenotypes and identify a stop-gain mutation in hgfa and two missense mutations in met by positional cloning from these zebrafish lines. The elongation of the thyroid primordium along the pharyngeal midline was dramatically disrupted in these zebrafish lines carrying a mutation in hgfa or met. Further studies show that MAPK inhibitor U0126 could mimic thyroid dysgenesis in zebrafish, and the phenotypes are rescued by overexpression of constitutively active MEK or Snail, downstream molecules of the HGF/Met pathway, in thyrocytes. Moreover, HGF promotes thyrocyte migration, which is probably mediated by downregulation of E-cadherin expression. The delayed bifurcation of the thyroid primordium is also observed in thyroid-specific Met knockout mice. Together, our findings reveal that HGF/Met is indispensable for the bifurcation of the thyroid primordium during thyroid development mediated by downregulation of E-cadherin in thyrocytes via MAPK-snail pathway.

Quantitative evaluation of the proximal contact area gap change characterization under intercuspal occlusion by intraoral 3D scanning: Food impaction with tight proximal contact.

OBJECTIVE: This study aimed to present three indicators that represent the proximal contact area gap change under intercuspal occlusion and to see if and how these indicators influence food impaction with tight proximal contact. MATERIALS AND METHODS: Ninety volunteers were recruited for bite force measurement and intraoral scanning. Three-dimensional surface data and buccal bite data were obtained for 60 impacted and 60 non-impacted teeth. The scanning data were imported into the Geomagic Studio 2013 to measure three indicators, which included the gap change maximum (Δdm, µm), the buccolingual position of Δdm (P), and the gap expanded buccolingual range (S, mm). The difference between two groups of three indicators and their relationship with food impaction with tight proximal contact were analyzed by the t test, the Pearson chi-squared test, the nonparametric Mann-Whitney U test, and the binary logistic regression analysis (a = 0.05). RESULTS: All indicators (Δdm, P, and S) were statistically different (p < 0.001, p = 0.002, and p < 0.001) in the impacted and non-impacted groups. Food impaction with tight proximal contact was affected by Δdm and S (p < 0.001, p = 0.039), but not by P (p = 0.409). CONCLUSION: The excessive increase of the gap change maximum and the gap expanded buccolingual range under bite force promoted the occurrence of food impaction with tight proximal contact. CLINICAL SIGNIFICANCE: The use of intraoral scanning to measure the characteristics of the proximal contact area gap change under bite force may help to deepen our understanding of the pathogenesis of food impaction with tight proximal contact. Importantly it can provide a reference basis for individualizing and quantifying occlusal adjustment treatment.

Regulating Sulfur Redox Kinetics by Coupling Photocatalysis for High-Performance Photo-Assisted Lithium-Sulfur Batteries.

Challenges such as shuttle effect have hindered the commercialization of lithium-sulfur batteries (LSBs), despite their potential as high-energy-density storage devices. To address these issues, we explore the integration of solar energy into LSBs, creating a photo-assisted lithium-sulfur battery (PA-LSB). The PA-LSB provides a novel and sustainable solution by coupling the photocatalytic effect to accelerate sulfur redox reactions. Herein, a perovskite quantum dot-loaded MOF material serves as a cathode for the PA-LSB, creating built-in electric fields at the micro-interface to extend the lifetime of photo-generated charge carriers. The band structure of the composite material aligns well with the electrochemical reaction potential of lithium-sulfur, enabling precise regulation of polysulfides in the cathode of the PA-LSB system. This is attributed to the selective catalysis of the liquid-solid reaction stage in the lithium-sulfur electrochemical process by photocatalysis. These contribute to the outstanding performance of PA-LSBs, particularly demonstrating a remarkably high reversible capacity of 679 mAh g-1 at 5 C, maintaining stable cycling for 1500 cycles with the capacity decay rate of 0.022% per cycle. Additionally, the photo-charging capability of the PA-LSB holds the potential to compensate for non-electric energy losses during the energy storage process, contributing to the development of lossless energy storage devices.

Super-Ionic Conductor Soft Filler Promotes Li+ Transport in Integrated Cathode-Electrolyte for Solid-State Battery at Room Temperature.

Composite polymer solid electrolytes (CPEs), possessing good rigid flexible, are expected to be used in solid-state lithium-metal batteries. The integration of fillers into polymer matrices emerges as a dominant strategy to improve Li+ transport and form a Li+-conducting electrode-electrolyte interface. However, challenges arise as traditional fillers: 1) inorganic fillers, characterized by high interfacial energy, induce agglomeration; 2) organic fillers, with elevated crystallinity, impede intrinsic ionic conductivity, both severely hindering Li+ migration. Here, a concept of super-ionic conductor soft filler, utilizing a Li+ conductivity nanocellulose (Li-NC) as a model, is introduced which exhibits super-ionic conductivity. Li-NC anchors anions, and enhances Li+ transport speed, and assists in the integration of cathode-electrolyte electrodes for room temperature solid-state batteries. The tough dual-channel Li+ transport electrolyte (TDCT) with Li-NC and polyvinylidene fluoride (PVDF) demonstrates a high Li+ transfer number (0.79) due to the synergistic coordination mechanism in Li+ transport. Integrated electrodes' design enables stable performance in LiNi0.5Co0.2Mn0.3O2|Li cells, with 720 cycles at 0.5 C, and 88.8% capacity retention. Furthermore, the lifespan of Li|TDCT|Li cells over 4000 h and Li-rich Li1.2Ni0.13Co0.13Mn0.54O2|Li cells exhibits excellent performance, proving the practical application potential of soft filler for high energy density solid-state lithium-metal batteries at room temperature.

The association between lymphocyte-to-monocyte ratio and all-cause mortality in obese hypertensive patients with diabetes and without diabetes: results from the cohort study of NHANES 2001-2018.

Objective: Obesity, hypertension and diabetes are high prevalent that are often associated with poor outcomes. They have become major global health concern. Little research has been done on the impact of lymphocyte-to-monocyte ratio (LMR) on outcomes in these patients. Thus, we aimed to explore the association between LMR and all-cause mortality in obese hypertensive patients with diabetes and without diabetes. Methods: The researchers analyzed data from the National Health and Nutrition Examination Survey (2001-2018), which included 4,706 participants. Kaplan-Meier analysis was employed to compare survival rate between different groups. Multivariate Cox proportional hazards regression models with trend tests and restricted cubic splines (RCS) analysis and were used to investigate the relationship between the LMR and all-cause mortality. Subgroup analysis was performed to assess whether there was an interaction between the variables. Results: The study included a total of 4706 participants with obese hypertension (48.78% male), of whom 960 cases (20.40%) died during follow-up (median follow-up of 90 months). Kaplan-Meier curves suggested a remarkable decrease in all-cause mortality with increasing LMR value in patients with diabetes and non-diabetes (P for log-rank test < 0.001). Moreover, multivariable Cox models demonstrated that the risk of mortality was considerably higher in the lowest quartile of the LMR and no linear trend was observed (P > 0.05). Furthermore, the RCS analysis indicated a non-linear decline in the risk of death as LMR values increased (P for nonlinearity < 0.001). Conclusions: Increased LMR is independently related with reduced all-cause mortality in patients with obese hypertension, regardless of whether they have combined diabetes.

Predicting preoperative muscle invasion status for bladder cancer using computed tomography-based radiomics nomogram.

OBJECTIVES: The aim of the study is to assess the efficacy of the established computed tomography (CT)-based radiomics nomogram combined with radiomics and clinical features for predicting muscle invasion status in bladder cancer (BCa). METHODS: A retrospective analysis was conducted using data from patients who underwent CT urography at our institution between May 2018 and April 2023 with urothelial carcinoma of the bladder confirmed by postoperative histology. There were 196 patients enrolled in all, and each was randomized at random to either the training cohort (n = 137) or the test cohort (n = 59). Eight hundred fifty-one radiomics features in all were retrieved. For feature selection, the significance test and least absolute shrinkage and selection operator (LASSO) approaches were utilized. Subsequently, the radiomics score (Radscore) was obtained by applying linear weighting based on the selected features. The clinical and radiomics model, as well as radiomics-clinical nomogram were all established using logistic regression. Three models were evaluated using analysis of the receiver operating characteristic curve. An area under the curve (AUC) and 95% confidence intervals (CI) as well as specificity, sensitivity, accuracy, negative predictive value, and positive predictive value were included in the analysis. Radiomics-clinical nomogram's performance was assessed based on discrimination, calibration, and clinical utility. RESULTS: After obtaining 851 radiomics features, 12 features were ultimately selected. Histopathological grading and tortuous blood vessels were included in the clinical model. The Radscore and clinical histopathology grading were among the final predictors in the unique nomogram. The three models had an AUC of 0.811 (95% CI, 0.742-0.880), 0.845 (95% CI, 0.781-0.908), and 0.896 (95% CI, 0.846-0.947) in the training cohort and in the test cohort they were 0.808 (95% CI, 0.703-0.913), 0.847 (95% CI, 0.739-0.954), and 0.887 (95% CI, 0.803-0.971). According to the DeLong test, the radiomics-clinical nomogram's AUC in the training cohort substantially differed from that of the clinical model (AUC: 0.896 versus 0.845, p = 0.015) and the radiomics model (AUC: 0.896 versus 0.811, p = 0.002). The Delong test in the test cohort revealed no significant difference among the three models. CONCLUSIONS: CT-based radiomics-clinical nomogram can be a useful tool for quantitatively predicting the status of muscle invasion in BCa.

High-Voltage Na0.76Ni0.25-x/2Mgx/2Mn0.75O2-xFx Cathode Improved by One-Step In Situ MgF2 Doping with Superior Low-Temperature Performance and Extra-Stable Air Stability.

P2-NaxMnO2 has garnered significant attention due to its favorable Na+ conductivity and structural stability for large-scale energy storage fields. However, achieving a balance between high energy density and extended cycling stability remains a challenge due to the Jahn-Teller distortion of Mn3+ and anionic activity above 4.1 V. Herein, we propose a one-step in situ MgF2 strategy to synthesize a P2-Na0.76Ni0.225Mg0.025Mn0.75O1.95F0.05 cathode with improved Na-storage performance and decent water/air stability. By partially substituting cost-effective Mg for Ni and incorporating extra F for O, the optimized material demonstrates both enhanced capacity and structure stability via promoting Ni2+/Ni4+ and oxygen redox activity. It delivers a high capacity of 132.9 mA h g-1 with an elevated working potential of ≈3.48 V and maintains ≈83.0% capacity retention after 150 cycles at 100 mA g-1 within 2-4.3 V, compared to the 114.9 mA h g-1 capacity and 3.32 V discharging potential of the undoped Na0.76Ni0.25Mn0.75O2. While increasing the charging voltage to 4.5 V, 133.1 mA h g-1 capacity and 3.55 V discharging potential (vs Na/Na+) were achieved with 72.8% capacity retention after 100 cycles, far beyond that of the pristine sample (123.7 mA h g-1, 3.45 V, and 43.8%@100 cycles). Moreover, exceptional low-temperature cycling stability is achieved, with 95.0% after 150 cycles. Finally, the Na-storage mechanism of samples employing various doping strategies was investigated using in situ EIS, in situ XRD, and ex situ XPS techniques.

First-In-Human Study on Pharmacokinetics, Safety, and Tolerability of Single and Multiple Escalating Doses of PA9159 Nasal Spray, a Highly Potent Glucocorticoid in Healthy Chinese Volunteers.

OBJECTIVE: PA9159 (previously named VSG159) is a structurally novel and highly potent glucocorticoid that plays a role in the late development of autoimmune and inflammatory diseases. The current first-in-human ascending-dose study of the PA9159 nasal spray was conducted in healthy Chinese volunteers to evaluate its pharmacokinetics, safety, and tolerability. In addition, the effects of PA9159 on serum cortisol secretion were investigated. METHODS: This was a double-blinded, randomized, placebo-controlled clinical study that included four single-dose groups in the single ascending dose cohort (SAD) and two multiple-dose groups in the multiple ascending dose cohort (MAD), with dose ranges of 10-80 µg and 20-40 µg, respectively. PA9159 was administered bilaterally via nasal spray once only or once daily for seven days. Pharmacokinetic, safety, and tolerability profiles were evaluated. RESULTS: A total of 60 participants completed the study. PA9159 doses of up to 80 µg in the SAD and up to 40 µg in the MAD were shown to be safe and tolerable. The most common treatment-related AEs were mild and transient local nasal AEs. Morning serum cortisol levels approximately remained unchanged in both the single-dose and multiple-dose groups. PA9159 was quantified in 41.8% (368/880) of the samples in all treatment groups, including 25.2% (105/416) of the SAD and 56.7% (263/464) of the MAD. The majority (>80.0%) of PA9159 plasma concentrations ranged from 0.5 to 2 pg/mL in determined samples. The mean AUC0-t of PA9159 in the SAD was 0.91, 1.39±0.68, 11.40±9.91, and 46.30±25.80 h*pg/mL in the 10 to 80 ug single group. The mean terminal half-life time (t1/2) was 8.43 h and 8.97±2.28 h in 40 ug and 80 ug single group, respectively. The mean AUCss of PA9159 in the MAD was 31.70±7.04, 44.20±20.60 h*pg /mL, and the t1/2 was 16.00±4.18 h, 21.20±10.20 h in the 20 ug and 40 ug multiple groups, respectively. The median Tmax was approximately 6 hours in both the SAD and MAD cohorts. CONCLUSIONS: The PA9159 nasal spray was generally safe and well tolerated, and the effects of PA9159 on serum cortisol levels were limited. The plasma concentration and systemic exposure to PA9159 were very low. These findings support the necessity for further clinical studies on PA9159 nasal spray in patients suffering from allergic rhinitis.

Gestational supplementation of Bifidobacterium, Lactobacillus, and Streptococcus thermophilus attenuates hepatic steatosis in offspring mice through promoting fatty acid ß-oxidation.

Currently, Bifidobacterium, Lactobacillus, and Streptococcus thermophilus (BLS) are widely recognized as the crucially beneficial bacteria in the gut. Many preclinical and clinical studies have shown their protective effects against non-alcoholic fatty liver disease (NAFLD). However, whether gestational BLS supplementation could alleviate NAFLD in the offspring is still unknown. Kunming mice were given a high-fat diet (HFD) for 4 weeks before mating. They received BLS supplementation by gavage during pregnancy. After weaning, offspring mice were fed with a regular diet up to 5 weeks old. Gestational BLS supplementation significantly increased the abundance of Actinobacteriota, Bifidobacterium, and Faecalibaculum in the gut of dams exposed to HFD. In offspring mice exposed to maternal HFD, maternal BLS intake significantly decreased the ratio of Firmicutes to Bacteroidetes as well as the relative abundance of Prevotella and Streptococcus, but increased the relative abundance of Parabacteroides. In offspring mice, maternal BLS supplementation significantly decreased the hepatic triglyceride content and mitigated hepatic steatosis. Furthermore, maternal BLS supplementation increased the glutathione content and reduced malondialdehyde content in the liver. In addition, mRNA and protein expression levels of key rate-limiting enzymes in mitochondrial ß-oxidation (CPT1α, PPARα, and PGC1α) in the livers of offspring mice were significantly increased after gestational BLS supplementation. Thus, gestational BLS supplementation may ameliorate maternal HFD-induced steatosis and oxidative stress in the livers of offspring mice by modulating fatty acid ß-oxidation.

Stabilizing the Bulk-Phase and Solid Electrolyte Interphase of Silicon Microparticle Anode by Constructing Gradient-Hierarchically Ordered Conductive Networks.

The poor bulk-phase and interphase stability, attributable to adverse internal stress, impede the cycling performance of silicon microparticles (µSi) anodes and the commercial application for high-energy-density lithium-ion batteries. In this work, a groundbreaking gradient-hierarchically ordered conductive (GHOC) network structure, ingeniously engineered to enhance the stability of both bulk-phase and the solid electrolyte interphase (SEI) configurations of µSi, is proposed. Within the GHOC network architecture, two-dimensional (2D) transition metal carbides (Ti3C2Tx) act as a conductive "brick", establishing a highly conductive inner layer on µSi, while the porous outer layer, composed of one-dimensional (1D) Tempo-oxidized cellulose nanofibers (TCNF) and polyacrylic acid (PAA) macromolecule, functions akin to structural "rebar" and "concrete", effectively preserves the tightly interconnected conductive framework through multiple bonding mechanisms, including covalent and hydrogen bonds. Additionally, Ti3C2Tx enhances the development of a LiF-enriched SEI. Consequently, the µSi-MTCNF-PAA anode presents a high discharge capacity of 1413.7 mAh g-1 even after 500 cycles at 1.0 C. Moreover, a full cell, integrating LiNi0.8Mn0.1Co0.1O2 with µSi-MTCNF-PAA, exhibits a capacity retention rate of 92.0% following 50 cycles. This GHOC network structure can offer an efficacious pathway for stabilizing both the bulk-phase and interphase structure of anode materials with high volumetric strain.

Challenges and Breakthroughs in Enhancing Temperature Tolerance of Sodium-Ion Batteries.

Lithium-based batteries (LBBs) have been highly researched and recognized as a mature electrochemical energy storage (EES) system in recent years. However, their stability and effectiveness are primarily confined to room temperature conditions. At temperatures significantly below 0 °C or above 60 °C, LBBs experience substantial performance degradation. Under such challenging extreme contexts, sodium-ion batteries (SIBs) emerge as a promising complementary technology, distinguished by their fast dynamics at low-temperature regions and superior safety under elevated temperatures. Notably, developing SIBs suitable for wide-temperature usage still presents significant challenges, particularly for specific applications such as electric vehicles, renewable energy storage, and deep-space/polar explorations, which requires a thorough understanding of how SIBs perform under different temperature conditions. By reviewing the development of wide-temperature SIBs, the influence of temperature on the parameters related to battery performance, such as reaction constant, charge transfer resistance, etc., is systematically and comprehensively analyzed. The review emphasizes challenges encountered by SIBs in both low and high temperatures while exploring recent advancements in SIB materials, specifically focusing on strategies to enhance battery performance across diverse temperature ranges. Overall, insights gained from these studies will drive the development of SIBs that can handle the challenges posed by diverse and harsh climates.