Organocatalyzed Asymmetric Conjugate Addition of Alcohols to ß-Fluoroalkyl Vinylsulfones by Bifunctional Phosphonium Salt Catalyst.

Chiral secondary alcohols, serving as essential structural motifs, hold significant potential for diverse applications. The exploration of effective synthetic strategies toward these compounds is both attractive and challenging. Herein, we present an asymmetric oxa-Michael reaction involving aliphatic alcohols as nucleophiles and ß-fluoroalkyl vinylsulfones catalyzed by bifunctional phosphonium salt (BPS), achieving high yields and excellent enantioselectivities (up to 98 % yield and 98 % ee). Additionally, a sequential process including asymmetric oxa-Michael and debenzylation, facilitated by BPS/Lewis acid cooperation, was revealed for synthesizing diverse chiral secondary alcohol compounds in high yields (81-88 %) with consistent stereoselectivities. Furthermore, mechanistic explorations and subsequent results unveiled that the enantioselectivity originates from hydrogen-bonding and ion-pair interactions between the BPS catalyst and the substrates.

Bulk and single-cell transcriptome reveal the immuno-prognostic subtypes and tumour microenvironment heterogeneity in HCC.

BACKGROUND & AIMS: Accumulating evidences suggest tumour microenvironment (TME) profoundly influence clinical outcome in hepatocellular carcinoma (HCC). Existing immune subtypes are susceptible to batch effects, and integrative analysis of bulk and single-cell transcriptome is helpful to recognize immune subtypes and TME in HCC. METHODS: Based on the relative expression ordering (REO) of 1259 immune-related genes, an immuno-prognostic signature was developed and validated in 907 HCC samples from five bulk transcriptomic cohorts, including 72 in-house samples. The machine learning models based on subtype-specific gene pairs with stable REOs were constructed to jointly predict immuno-prognostic subtypes in single-cell RNA-seq data and validated in another single-cell data. Then, cancer characteristics, immune landscape, underlying mechanism and therapeutic benefits between subtypes were analysed. RESULTS: An immune-related signature with 29 gene pairs stratified HCC samples individually into two risk subgroups (C1 and C2), which was an independent prognostic factor for overall survival. The machine learning models verified the immune subtypes from five bulk cohorts to two single-cell transcriptomic data. Integrative analysis revealed that C1 had poorer outcomes, higher CNV burden and malignant scores, higher sensitivity to sorafenib, and exhibited an immunosuppressive phenotype with more regulators, e.g., myeloid-derived suppressor cells (MDSCs), Mø_SPP1, while C2 was characterized with better outcomes, higher metabolism, more benefit from immunotherapy, and displayed active immune with more effectors, e.g., tumour infiltrating lymphocyte and dendritic cell. Moreover, both two single-cell data revealed the crosstalk of SPP1-related L-R pairs between cancer and immune cells, especially SPP1-CD44, might lead to immunosuppression in C1. CONCLUSIONS: The REO-based immuno-prognostic subtypes were conducive to individualized prognosis prediction and treatment options for HCC. This study paved the way for understanding TME heterogeneity between immuno-prognostic subtypes of HCC.

TREM2-dependent microglial function is essential for remyelination and subsequent neuroprotection.

Disability in multiple sclerosis (MS) is driven in part by the failure of remyelination and progressive neurodegeneration. Microglia, and specifically triggering receptor expressed on myeloid cells 2 (TREM2), a factor highly expressed in microglia, have been shown to play an important role in remyelination. Here, using a focal demyelination model in the brain, we demonstrate that demyelination is persistent in TREM2 knockout mice, lasting more than 6 weeks after lysolecithin injection and resulting in substantial neurodegeneration. We also find that TREM2 knockout mice exhibit an altered glial response following demyelination. TREM2 knockout microglia demonstrate defects in migration and phagocytosis of myelin debris. In addition, human monocyte-derived macrophages from subjects with a TREM2 mutation prevalent in human disease also show a defect in myelin debris phagocytosis. Together, we highlight the central role of TREM2 signaling in remyelination and neuroprotection. These findings provide insights into how chronic demyelination might lead to axonal damage and could help identify novel neuroprotective therapeutic targets for MS.

Effect of chemotherapy and different chemotherapy regimens on bone health among Chinese breast cancer women in different menstrual status: a self-control study.

PURPOSE: Although the therapy-related bone loss attracts increasing attention nowadays, the differences in chemotherapy-induced bone loss and bone metabolism indexes change among breast cancer (BC) women with different menstrual statuses or chemotherapy regimens are unknown. The aim of the study is to explore the effects of different regimens of chemotherapy on bone health. METHOD: The self-control study enrolled 118 initially diagnosed BC women without distant metastasis who underwent dual-energy X-ray absorptiometry (DXA) bone mineral density (BMD) screening and (or) bone metabolism index monitoring during chemotherapy at Chongqing Breast Cancer Center. Mann-Whitney U test, Cochran's Q test, and Wilcoxon sign rank test were performed. RESULTS: After chemotherapy, the BMD in the lumbar 1-4 and whole lumbar statistically decreased (- 1.8%/per 6 months), leading to a significantly increased proportion of osteoporosis (27.1% vs. 20.5%, P < 0.05), which were mainly seen in the premenopausal group (- 7.0%/per 6 months). Of the chemotherapeutic regimens of EC (epirubicin + cyclophosphamide), TC (docetaxel + cyclophosphamide), TEC (docetaxel + epirubicin + cyclophosphamide), and EC-T(H) [epirubicin + cyclophosphamide-docetaxel and/or trastuzumab], EC regimen had the least adverse impact on BMD, while the EC-TH regimen reduced BMD most (P < 0.05) inspite of the non-statistical difference between EC-T regimen, which was mainly seen in the postmenopausal group. Chemotherapy-induced amenorrhea (estradiol 94 pg/ml vs, 22 pg/ml; FSH 9.33 mIU/ml vs. 61.27 mIU/ml) was proved in premenopausal subgroup (P < 0.001). Except the postmenopausal population with calcium/VitD supplement, the albumin-adjusted calcium increased significantly (2.21 mmol/l vs. 2.33 mmol/l, P < 0.05) after chemotherapy. In postmenopausal group with calcium/VitD supplement, ß-CTX decreased significantly (0.56 ng/ml vs. 0.39 ng/ml, P < 0.05) and BMD were not affected by chemotherapy (P > 0. 05). In premenopausal group with calcium/VitD supplement, PTH decreased significantly (52.90 pg/ml vs. 28.80 pg/ml, P = 0. 008) and hip BMD increased after chemotherapy (0.845 g/m2 vs. 0.952 g/m2, P = 0. 006). As for both postmenopausal and premenopausal group without calcium/VitD supplement, there was a significant decrease in bone mass in hip and lumbar vertebrae after chemotherapy (0.831 g/m2 vs. 0.776 g/m2; 0.895 g/m2 vs. 0.870 g/m2, P < 0.05). CONCLUSION: Chemotherapy might induce lumbar vertebrae BMD loss and spine osteoporosis with regimen differences among Chinese BC patients. Calcium/VitD supplementation could improve bone turnover markers, bone metabolism indicators, and bone mineral density. Early interventions on bone health are needed for BC patients during chemotherapy.

A Strong-Acid-Resistant [Th6 ] Cluster-Based Framework for Effectively and Size-Selectively Catalyzing Reductive Amination of Aldehydes with N,N-Dimethylformamide.

Utilization of N,N-dimethylformamide (DMF) as an amine source and reductant for synthesizing tertiary amines is a promising way to replace the substrates formaldehyde and dimethylamine, and it is desirable to seek porous acid-resistant catalysts for heterogeneous catalysis of this reaction. Herein, a robust metal-organic framework (MOF) {[Th6 O4 (OH)4 (H2 O)6 (BCP)3 ]⋅10 DMF}n (1) containing stacked nanocages with a diameter of 1.55 nm was constructed. Compound 1 can maintain its single-crystal structure even kept in air at 400 °C for 3 h, and in DMF or water at 200 °C for 7 days. Density functional theory (DFT) calculations suggested that the high interaction energy between the [Th6 O4 (OH)4 (H2 O)6 ]12+ clusters and ligands was responsible for the excellent stability of 1. Catalytic investigations revealed that 1 can effectively and size-selectively catalyze the reductive amination of aldehydes with DMF, and it can be reused at least five times without obvious loss in catalytic activity.

Highly Strained Oxygen-Doped Chiral Molecular Belts of the Zigzag-Type with Strong Circularly Polarized Luminescence.

Herein we report a two-directional cyclization strategy for the synthesis of highly strained depth-expanded oxygen-doped chiral molecular belts of the zigzag-type. From the easily accessible resorcin[4]arenes, an unprecedented cyclization cascade generating fused 2,3-dihydro-1H-phenalenes has been developed to access expanded molecular belts. Stitching up the fjords through intramolecular nucleophilic aromatic substitution and ring-closing olefin metathesis reactions furnished a highly strained O-doped C2 -symmetric belt. The enantiomers of the acquired compounds exhibited excellent chiroptical properties. The calculated parallelly aligned electric (µ) and magnetic (m) transition dipole moments are translated to the high dissymmetry factor (|glum | up to 0.022). This study provides not only an appealing and useful strategy for the synthesis of strained molecular belts but also a new paradigm for the fabrication of belt-derived chiroptical materials with high CPL activities.

Population-specific cut-off points of fatty liver index: a study based on the National Health and Nutrition Examination Survey data.

BACKGROUND: Fatty liver index (FLI) is the most recognized blood biomarker for diagnosis of hepatic steatosis (HS), but lacks the reliable specific cut-off points (COPs). Therefore, we aim to investigate the population-specific COPs of FLI based on the results of liver ultrasound transient elastography (LUTE) and conventional ultrasonography in the National Health and Nutrition Examination Survey (NHANES). METHODS: 5948 participants who underwent LUTE from the NHANES 2017-2018 and 14,797 participants who underwent conventional ultrasonography from the Third NHANES (NHANES III) were recruited. FLI was calculated by using body mass index (BMI), waist circumference (WC), triglyceride, and gamma-glutamyl transferase, and its optimal COPs in a specific population (stratified by sex, BMI, and WC) were obtained from receiver operator characteristics (ROC) curve with ultrasonic-diagnosed HS as the reference standard. RESULTS: Based on LUTE in NHANES 2017-2018, the prevalence of HS and metabolic dysfunction-associated fatty liver disease (MAFLD) were 58.7% and 56.2%, respectively, and the optimal COP of FLI for HS diagnosis in the overall population was 45.60, with an area under ROC curve (AUROC) of 0.833 (0.822-0.844). Based on conventional ultrasonography in NHANES III, the prevalence of HS and MAFLD were 34.4% and 27. 9%, respectively, and the optimal COP of FLI for HS was 59.5, with an AUROC of 0.681 (0.671-0.691). With the increase of BMI and WC, the COPs increased gradually with significant differences between different groups. Compared with conventional ultrasonography, the COPs of FLI based on LUTE were much more precise, with higher diagnostic ability. The population-specific COPs of FLI stratified by gender, WC, and BMI were tabulated. CONCLUSION: In the United States, the incidences of HS and MAFLD were high, especially when assessed by LUTE. The FLI based on LUTE is well capable of predicting HS when stratified by gender, WC, and BMI.

Risk factors and consequences of conversion in minimally invasive distal pancreatectomy.

Background: Although recent studies have reported potential benefits of laparoscopic approach in distal pancreatectomy, reports of conversion during minimally invasive distal pancreatectomy (MIDP) were limited. Methods: This was a retrospective study using data from Sir Run Run Shaw Hospital around May 2013 to December 2018. Outcomes of patients who had conversions during MIDP were compared with patients with successful MIDP and with patients undergoing open distal pancreatectomy (ODP). Results: Two-hundred and eighty-three cases were included in this study: 225 (79.5%) had MIDP, 30 (10.6%) had conversions and 28 (9.9%) had outpatient department. The risk factors for conversion included large lesion size (heart rates [HR]: 5.632, 95% confidencevinterval [CI]: 1.036-1.450, P = 0.018) and pancreatic cancer (HR: 6.957, 95% CI: 1.359-8.022, P = 0.009). Compared with MIDP, those who required conversion were associated with longer operations (P = 0.003), higher blood loss (P < 0.001) and more severe of the complications (P < 0.001). However, no statistically significant differences were found between the conversion group and ODP. Conclusions: Large lesion size and pancreatic cancer were reported to be independent risk factors for conversion during MIDP. As for post-operative outcomes, the outcomes of successfully MIDP were better than those for conversion. However, conversion did not lead to worsening outcomes when compared with ODP.

Highly Enantioselective Synthesis of Phosphorus-Containing ϵ-Benzosultams by Bifunctional Phosphonium Salt-Promoted Hydrophosphonylation.

ϵ-Benzosultam derivatives are potential drug candidates with diverse biological activities. A series of chiral ϵ-benzosultams bearing phosphorus functionalities was synthesized by catalytic asymmetric hydrophosphonylation in the presence of a bifunctional phosphonium salt catalyst. The desired hydrophosphonylation products were obtained in good yields with high enantioselectivities, and scale-up reactions and further derivations were successfully accomplished. Some control experiments were also conducted to elucidate the plausible reaction mechanism of this chemical transformation.

Expanded Inverse-Sandwich Complexes of Lanthanum Borides: La2B10- and La2B11.

Inverse-sandwich structures have been observed recently for dilanthanide boride clusters, in which two Ln atoms sandwich a monocyclic Bx ring for x = 7-9. An interesting question is if larger Bx rings are possible to form such inverse-sandwich clusters. Here we address this question by investigating La2B10- and La2B11- using photoelectron spectroscopy and ab initio quantum chemical calculations. Photoelectron spectra of La2B10- and La2B11- show complicated, but well-resolved, spectral features that are used to compare with theoretical calculations. We have found that global minimum structures of the two clusters are based on the octa-boron ring. The global minimum of La2B10- consists of two chiral enantiomers with C1 symmetry, which can be viewed as adding a B2 unit off-plane to the B8 ring, whereas that of La2B11- can be viewed as adding a B3 unit in-plane to the B8 ring in a second coordination shell. Chemical bonding analyses reveal localized B-B bonds on the edge of the clusters and delocalized bonds in the expanded boron frameworks. The interactions between the La atoms and the boron frameworks include the unique (d-p)δ bonding, which was found to be the key for inverse-sandwich complexes with monocyclic boron rings. The current study confirms that the largest monocyclic boron ring to form the inverse-sandwich structures is B9 and provide insights into the structural evolutions of larger lanthanide boride clusters.

Laparoscopic procedure is associated with lower morbidity for simultaneous resection of colorectal cancer and liver metastases: an updated meta-analysis.

BACKGROUND: It has been demonstrated that simultaneous resection of both primary colorectal lesion and metastatic hepatic lesion is a safe approach with low mortality and postoperative complication rates. However, there are some controversies over which kind of surgical approach is better. The aim of study was to compare the efficacy and safety of laparoscopic surgeries and open surgeries for simultaneous resection of colorectal cancer (CRC) and synchronous colorectal liver metastasis (SCRLM). METHODS: A systemic search of online database including PubMed, Web of Science, Cochrane Library, and Embase was performed until June 5, 2019. Intraoperative complications, postoperative complications, and long-term outcomes were synthesized by using STATA, version 15.0. Cumulative and single-arm meta-analyses were also conducted. RESULTS: It contained twelve studies with 616 patients (273 vs 343, laparoscopic surgery group and open surgery group, respectively) and manifested latest surgical results for the treatment of CRC and SCRLM. Among patients who underwent laparoscopic surgeries, they had lower rates of postoperative complications (OR = 0.66, 95% CI: 0.46 to 0.96, P = 0.028), less intraoperative blood loss (weight mean difference (WMD) = - 113.31, 95% CI: - 189.03 to - 37.59, P = 0.003), less time in the hospital and recovering after surgeries (WMD = - 2.70, 95% CI: - 3.99 to - 1.40, P = 0.000; WMD = - 3.20, 95% CI: - 5.06 to - 1.34, P = 0.001), but more operating time (WMD = 36.57, 95% CI: 7.80 to 65.35, P = 0.013). Additionally, there were no statistical significance between two kinds of surgical approaches in disease-free survival and overall survival. Moreover, cumulative meta-analysis indicated statistical difference in favor of laparoscopic surgery in terms of morbidity was firstly detected in the 12th study in 2018 (OR = 0.66, 95% CI: 0.46 to 0.96, P = 0.028) as the 95% CI narrowed. CONCLUSION: Compared with open surgeries, laparoscopic surgeries are safer (postoperative complications and intraoperative blood loss) and more effective (length of hospital stay and postoperative stay), and it can be considered as the first option for management of SCRLM in high-volume laparoscopic centers. TRIAL REGISTRATION: CRD42020151176.

Agro-ecological suitability assessment of Chinese Medicinal Yam under future climate change.

Chinese Medicinal Yam (CMY) has been prescribed as medicinal food for thousand years in China by Traditional Chinese Medicine (TCM) practitioners. Its medical benefits include nourishing the stomach and spleen to improve digestion, replenishing lung and kidney, etc., according to the TCM literature. As living standard rises and public health awareness improves in recent years, the potential medicinal benefits of CMY have attracted increasing attention in China. It has been found that the observed climate change in last several decades, together with the change in economic structure, has driven significant shift in the pattern of the traditional CMY planting areas. To identify suitable planting area for CMY in the near future is critical for ensuring the quality and supply quantity of CMY, guiding the layout of CMY industry, and safeguarding the sustainable development of CMY resources for public health. In this study, we first collect 30-year records of CMY varieties and their corresponding phenology and agro-meteorological observations. We then consolidate these data and use them to enrich and update the eco-physiological parameters of CMY in the agro-ecological zone (AEZ) model. The updated CMY varieties and AEZ model are validated using the historical planting area and production under observed climate conditions. After the successful validation, we use the updated AEZ model to simulate the potential yield of CMY and identify the suitable planting regions under future climate projections in China. This study shows that regions with high ecological similarity to the genuine and core producing areas of CMY mainly distribute in eastern Henan, southeastern Hebei, and western Shandong. The climate suitability of these areas will be improved due to global warming in the next 50 years, and therefore, they will continue to be the most suitable CMY planting regions.

Muscle specific kinase (MuSK) activation preserves neuromuscular junctions in the diaphragm but is not sufficient to provide a functional benefit in the SOD1G93A mouse model of ALS.

Amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting motor neurons, is characterized by rapid decline of motor function and ultimately respiratory failure. As motor neuron death occurs late in the disease, therapeutics that prevent the initial disassembly of the neuromuscular junction may offer optimal functional benefit and delay disease progression. To test this hypothesis, we treated the SOD1G93A mouse model of ALS with an agonist antibody to muscle specific kinase (MuSK), a receptor tyrosine kinase required for the formation and maintenance of the neuromuscular junction. Chronic MuSK antibody treatment fully preserved innervation of the neuromuscular junction when compared with control-treated mice; however, no preservation of diaphragm function, motor neurons, or survival benefit was detected. These data show that anatomical preservation of neuromuscular junctions in the diaphragm via MuSK activation does not correlate with functional benefit in SOD1G93A mice, suggesting caution in employing MuSK activation as a therapeutic strategy for ALS patients.

Serotype, antimicrobial susceptibility and genotype profiles of Salmonella isolated from duck farms and a slaughterhouse in Shandong province, China.

BACKGROUND: Salmonella has been considered as one of the most important foodborne pathogens that threatened breeding industry and public health. To investigate the prevalence and characterization of Salmonella isolated from duck farms and a slaughterhouse in Shandong province, a total of 49 Salmonella strains were isolated from 2342 samples from four duck farms and one duck slaughterhouse in Jinan and Tai'an, Shandong province, China. RESULTS: Among the isolates, S. Enteritidis (20/49, 40.8%) and S. Anatum (10/49, 20.4%) were the most prevalent, and high resistance rates were detected for erythromycin (49/49, 100.0%) and nalidixic acid (47/49, 95.9%). Class I integrons were detected in 17 isolates (34.7%17/49), which contained gene cassettes aadA7 + aac3-Id(15/17) and aadA5 + dfrA17 (2/17). Eleven different kinds of resistance genes were detected while blaTEM(36/49, 73.5%) was the most prevalent, followed by sul2(14/49, 28.6%). Thirteen virulence genes were tested, and all of the strains carried invA, hilA and sipA. Multilocus sequence typing (MLST) results showed that seven sequence types (STs) were identified; ST11 was the most prevalent ST (20/49, 40.8%), followed by ST2441 (10/49, 20.4%). There was a strong correlation between STs and serovars. The results of pulsed field gel electrophoresis(PFGE) showed that 39 PFGE patterns were generated from 49 Salmonella strains. PFGE patterns were mostly diverse and revealed high similarity between the isolates from the same sampling sites. CONCLUSIONS: The presence of Salmonella infections among duck farms revealed that ducks could also be potential reservoirs for Salmonella. The high resistance rates against commonly used antimicrobials suggested a need for more reasonable use of antimicrobials, as well as for investigating substitutes for antimicrobials.

DLK initiates a transcriptional program that couples apoptotic and regenerative responses to axonal injury.

The cell intrinsic factors that determine whether a neuron regenerates or undergoes apoptosis in response to axonal injury are not well defined. Here we show that the mixed-lineage dual leucine zipper kinase (DLK) is an essential upstream mediator of both of these divergent outcomes in the same cell type. Optic nerve crush injury leads to rapid elevation of DLK protein, first in the axons of retinal ganglion cells (RGCs) and then in their cell bodies. DLK is required for the majority of gene expression changes in RGCs initiated by injury, including induction of both proapoptotic and regeneration-associated genes. Deletion of DLK in retina results in robust and sustained protection of RGCs from degeneration after optic nerve injury. Despite this improved survival, the number of axons that regrow beyond the injury site is substantially reduced, even when the tumor suppressor phosphatase and tensin homolog (PTEN) is deleted to enhance intrinsic growth potential. These findings demonstrate that these seemingly contradictory responses to injury are mechanistically coupled through a DLK-based damage detection mechanism.

HIV transmission and related risk factors among serodiscordant couples in Liuzhou, China.

To evaluate the incidence and risk factors for human immunodeficiency virus (HIV) seroconversion of HIV-negative partners among HIV-discordant couples in Liuzhou, China, 1854 eligible HIV-serodiscordant couples were retrospectively identified through the HIV epidemiology and follow-up database from January 1, 1996 to June 30, 2013. Cox proportional-hazards model was used to examine risk factors related to HIV seroconversion of negative partners. Finally, 125 HIV seroconversion occurred over 4963.5 person-years, resulting in an overall HIV incidence of 2.52/100 person-years. HIV-positive partners with the last CD4 counts of 350 cells/ul or more were significantly protected against HIV seroconversion compared with those CD4 counts of less than 200 cells/ul (aHR = 0.46, 95% CI: 0.27-0.81, P < 0.01). Men with HIV-positive wives (aHR: 1.96, 95% CI: 1.27-3.02, P < 0.01), HIV-positive partners who did not receive ART before their HIV-negative partners' seroconversion (aHR: 2.22, 95% CI, 1.41-3.51, P < 0.01) and patients reported intermittent condom use (aHR: 7.60, 95% CI, 4.37-13.21, P < 0.01) were associated with increased risk of HIV seroconversion. HIV-negative partners remain high risk of HIV infection in Liuzhou city. Comprehensive package of HIV prevention services should contribute to reduction in HIV transmission of discordant couples.

Optimization of cobalt-based MOFs for super-capacitor electrode materials of new energy vehicle.

Super-capacitors (SCs), as new energy conversion storage elements, have attracted much attention, but there is still a research gap in the design of electrode materials. In this study, the optimization scheme of Metal-Organic Frameworks (MOFs) and cobalt-based MOF composites as electrode materials for SCs in new energy vehicles is explored, and a series of experiments are conducted to evaluate their performance. Scanning Electron Microscope (SEM) images reveal that the cobalt-based MOF composites have a surface morphology of particles with uniform distribution. The electrochemical performance test results show that the specific capacitance of the cobalt-based MOF composites is much higher than the sum of the two individual electrode materials and presents a remarkable increase with the scanning rate. Additionally, in the constant current charge-discharge test, cobalt-based MOF composites exhibit the longest charge-discharge time and good symmetry. Electrolyte particle contact tests for samples at different preparation temperatures display that high-temperature samples have better structural stability and electrolyte ion contact. In Cyclic Voltammetry (CV) and Galvanostatic Charge Discharge (GCD) tests, the 250 °C sample demonstrates the best electrochemical properties and the highest specific capacitance (269 F/g). Moreover, as the current density increases, the specific capacitance of the 600 °C sample decreases at a lower rate, showing stronger stability. However, the use of cobalt-based MOF materials may pose environmental and safety risks, such as the environmental impact of cobalt resource mining, instability under high-temperature conditions, and the possible production of hazardous substances. Therefore, these factors need to be fully considered when designing and using SCs to ensure the environmental friendliness and safety of cobalt-based MOFs. These results provide an important reference for selecting and optimizing electrode materials for SCs in new energy vehicles. Furthermore, this study offers research suggestions for improving new energy materials, filling the research gaps in related fields, and supporting the further development of SC technology.

Preparation of Puerarin Long Circulating Liposomes and its Effect on Osteoporosis in Castrated Rats.

Osteoporosis is a disease that causes low bone mass and deterioration of bone microarchitecture. Puerarin is a natural isoflavone compound that has been shown to possess anti-inflammatory, antioxidant and ameliorative effects on osteoporosis with less adverse reactions. However, its fast metabolism and low oral bioavailability limit its application. This study aimed to prepare d-α-tocopherol polyethylene glycol 1000 succinate (TPGS)- modified Puerarin Long Circulating Liposomes (TPGS-Puerarin-liposomes), in order to improve the oral bioavailability of puerarin, before evaluation of its pharmacological activity in vitro and in vivo. We employed film dispersion method to develop TPGS-Puerarin-liposomes before appropriate characterizations. Afterwards, we utilized in vivo imaging, pharmacokinetic analysis and in vitro drug release testing to further evaluate the in vivo and in vitro delivery efficiency. In addition, we established a castrated osteoporosis rat model to observe the changes in femur tissue structure and bone micromorphology via hematoxylin-eosin (HE) staining and Micro Computed Tomography (Micro CT). Besides, levels of oxidative stress and inflammatory indicators, as well as expression of wnt/ß-catenin pathway-related proteins were detected. In terms of physiochemical properties, the respective mean particle size (PS) and zeta potential (ZP) of TPGS-Puerarin-liposomes were 76.63±0.59 nm and -25.54±0.11 mV. The liposomal formulation exhibited encapsulation efficiency (EE) of 95.08±0.25% and drug loading (DL) of 7.84±0.07%, along with excellent storage stability. Compared with free drugs, the TPGS-Puerarin-liposomes demonstrated a sustained release effect and could increase blood concentration of puerarin in rats, thereby significantly improving its bioavailability. Also, in vivo studies have confirmed potential of the liposomes to promote bone tissue targeting and accumulation of puerarin, coupled with significant improvement of the osteoporotic status. Besides, the liposomes could also reduce levels of oxidative stress and inflammatory factors in serum and bone tissue. Additionally, we discovered that TPGS-Puerarin-liposomes increased Wnt, ß-catenin and T-cell factor (TCF) expressions at protein level in the wnt/ß-catenin signaling pathway. This study has demonstrated the potential of TPGS-Puerarin-liposomes for treatment of osteoporosis.