First-line treatment of severe aplastic anemia: immunosuppressive therapy plus eltrombopag versus haploidentical hematopoietic stem cell transplantation, a multicenter prospective study.

Matched-related donor hematopoietic stem cell transplantation (HSCT) remains the preferred first-line option for severe aplastic anemia (SAA) patients aged <40 years even in the era of eltrombopag (EPAG). However, there has not been any direct comparison between immunosuppressive therapy (IST) plus EPAG (IST + EPAG) and haploidentical HSCT (Haplo-HSCT) as first-line therapy. This study prospectively compared the efficacy, safety and health-related quality of life (HRQoL) of Haplo-HSCT (n = 147) and IST + EPAG (n = 121) as first-line treatment for patients with SAA. The results showed that 86.3% of patients in the Haplo-HSCT group and 24.1% of patients in the IST + EPAG group achieved normal complete blood count (CBC) (P < 0.001) after 6 months of treatment. The time to achieve transfusion independence and absolute neutrophil count ≥ 1.0 × 109/L were shorter in the Haplo-HSCT group than in the IST + EPAG group (P < 0.05). In the IST + EPAG and Haplo-HSCT, 3-year overall survival (OS) was 92.4 ± 2.4% and 82.8 ± 3.1% (P = 0.017), whereas 3-year failure-free survival (FFS) was 69.4 ± 4.2% and 81.6 ± 3.2% (P = 0.002), respectively. Similar results were observed in patients with <40 years of age. Among patients with ≥40 years of age, there was no difference in 3-year OS (88.6 ± 4.8% vs. 82.4 ± 8.1%, P = 0.517) between the IST + EPAG and Haplo-HSCT groups, whereas 3-year FFS was lower in the IST + EPAG (58.7 ± 7.5% vs. 82.4 ± 8.1%, P = 0.043). Subgroup analysis for populations aged <40 years indicated that SAA benefited more from IST + EPAG, and very SAA (vSAA) benefited more from Haplo-HSCT. Patients treated with haplo-HSCT scored significantly better in the HRQoL than treated with IST + EPAG (P < 0.0001). Multivariate analysis showed that first-line Haplo-HSCT was associated with normal CBC at 6 months, better FFS and led to a better HRQoL (P < 0.001). In summary, the IST + EPAG achieved better OS for <40 years SAA patients, while the Haplo-HSCT accelerated hematopoietic recovery and HRQoL, achieved better FFS even for those <40 years vSAA and ≥40 years patients.

Comparison of efficacy of eltrombopag combined with immunosuppression in the treatment of severe aplastic anemia and very severe aplastic anemia: real-world data and evidence.

Eltrombopag combined with immunosuppressive therapy (IST) was superior to IST alone for severe aplastic anemia (SAA) in the previous studies. But in China, horse antithymocyte globulin (hATG) is not available, instead, we use rabbit ATG (rATG). Here, we compared the efficacy and safety of IST (rATG combined with cyclosporine) combined with or without eltrombopag for the first-line treatment of SAA and very severe aplastic anemia (VSAA). A total of 371 patients in ten institutions in China from April 1, 2017 to December 1, 2022 were enrolled. The overall response (OR) rate at 3 months (54.2% vs. 41%; P = 0.046), the complete response (CR) (31.3% vs. 19.4%; P = 0.041) and OR (78.3% vs. 51.1%; P < 0.0001) rates at 6 months were significantly higher with IST combined with eltrombopag than with IST alone in SAA patients. While in VSAA patients, the addition of eltrombopag to IST only increased the CR rate at 6 months (29.8% vs. 9.43%; P = 0.010). Liver injury increased significantly in groups treated with IST combined with eltrombopag (P < 0.05). Serious treatment-related toxicities were similar (P > 0.05). In patients with SAA, 3-year failure-free survival (FFS) of eltrombopag combined with IST group was significantly higher than that of IST group (70.7 ± 5.3% vs. 50.3 ± 3.9%; P = 0.007). In patients with VSAA, the addition of eltrombopag significantly improved 3-year overall survival (OS) (82.2 ± 5.7% vs. 57.3 ± 7.2%; P = 0.020). Our findings suggested that IST combined with eltrombopag could improve the hematological recovery of newly diagnosed SAA without increasing severe toxicities. But in VSAA, the addition of eltrombopag seemed to show no other improvement to efficacy except the CR rate at 6 months.

Effect and mechanism of Qingre Huashi decoction on drug-resistant Helicobacter pylori.

BACKGROUND: Helicobacter pylori (HP), the most common pathogenic microorganism in the stomach, can induce inflammatory reactions in the gastric mucosa, causing chronic gastritis and even gastric cancer. HP infection affects over 4.4 billion people globally, with a worldwide infection rate of up to 50%. The multidrug resistance of HP poses a serious challenge to eradication. It has been de-monstrated that compared to bismuth quadruple therapy, Qingre Huashi decoction (QHD) combined with triple therapy exhibits comparable eradication rates but with a lower incidence of adverse reactions; in addition, QHD can directly inhibit and kill HP in vitro. AIM: To explore the effect and mechanism of QHD on clinically multidrug-resistant and strong biofilm-forming HP. METHODS: In this study, 12 HP strains were isolated in vitro after biopsy during gastroscopy of HP-infected patients. In vitro, the minimum inhibitory concentration (MIC) values for clinical HP strains and biofilm quantification were determined through the E-test method and crystal violet staining, respectively. The most robust biofilm-forming strain of HP was selected, and QHD was evaluated for its inhibitory and bactericidal effects on the strain with strong biofilm formation. This assessment was performed using agar dilution, E-test, killing dynamics, and transmission electron microscopy (TEM). The study also explored the impact of QHD on antibiotic resistance in these HP strains with strong biofilm formation. Crystalline violet method, scanning electron microscopy, laser confocal scanning microscopy, and (p)ppGpp chromatographic identification were employed to evaluate the effect of QHD on biofilm in strong biofilm-forming HP strains. The effect of QHD on biofilm and efflux pump-related gene expression was evaluated by quantitative polymerase chain reaction. Non-targeted metabolomics with UHPLC-MS/MS was used to identify potential metabolic pathways and biomarkers which were different between the NC and QHD groups. RESULTS: HP could form biofilms of different degrees in vitro, and the intensity of formation was associated with the drug resistance of the strain. QHD had strong bacteriostatic and bactericidal effects on HP, with MICs of 32-64 mg/mL. QHD could inhibit the biofilm formation of the strong biofilm-forming HP strains, disrupt the biofilm structure, lower the accumulation of (p)ppGpp, decrease the expression of biofilm-related genes including LuxS, Spot, glup (HP1174), NapA, and CagE, and reduce the expression of efflux pump-related genes such as HP0605, HP0971, HP1327, and HP1489. Based on metabolomic analysis, QHD induced oxidative stress in HP, enhanced metabolism, and potentially inhibited relevant signaling pathways by upregulating adenosine monophosphate (AMP), thereby affecting HP growth, metabolism, and protein synthesis. CONCLUSION: QHD exerts bacteriostatic and bactericidal effects on HP, and reduces HP drug resistance by inhibiting HP biofilm formation, destroying its biofilm structure, inhibiting the expression of biofilm-related genes and efflux pump-related genes, enhancing HP metabolism, and activating AMP in HP.

Palladium-Catalyzed Cascade Carbonylation Reaction: Synthesis of Fused Isoindolinones.

A palladium-catalyzed cascade carbonylation reaction of 2-bromo-N-(2-iodophenyl)benzamides with benzylidenecyclopropanes for the synthesis of fused isoindolinone derivatives has been developed. A broad range of 6/5/6/6 tetracyclic isoindolinone products were efficiently prepared in moderate to good yields with diverse substitution. Two carbonyl groups were incorporated into the substrates in a single step with the formation of four carbon-carbon bonds and two carbon-heteroatom bonds.

Focus on seed cells: stem cells in 3D bioprinting of corneal grafts.

Corneal opacity is one of the leading causes of severe vision impairment. Corneal transplantation is the dominant therapy for irreversible corneal blindness. However, there is a worldwide shortage of donor grafts and consequently an urgent demand for alternatives. Three-dimensional (3D) bioprinting is an innovative additive manufacturing technology for high-resolution distribution of bioink to construct human tissues. The technology has shown great promise in the field of bone, cartilage and skin tissue construction. 3D bioprinting allows precise structural construction and functional cell printing, which makes it possible to print personalized full-thickness or lamellar corneal layers. Seed cells play an important role in producing corneal biological functions. And stem cells are potential seed cells for corneal tissue construction. In this review, the basic anatomy and physiology of the natural human cornea and the grafts for keratoplasties are introduced. Then, the applications of 3D bioprinting techniques and bioinks for corneal tissue construction and their interaction with seed cells are reviewed, and both the application and promising future of stem cells in corneal tissue engineering is discussed. Finally, the development trends requirements and challenges of using stem cells as seed cells in corneal graft construction are summarized, and future development directions are suggested.

Therapeutic effect of nicotinamide mononucleotide on Alzheimer's disease through activating autophagy and anti-oxidative stress.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of ß-amyloid (Aß) plaques and neurofibrillary tangles composed of tau protein in the brain. These neuropathological hallmarks contribute to cognitive impairment by inducing neuronal loss in the cerebral cortex and hippocampus. Unfortunately, current therapeutic approaches only target symptomatic relief and do not impede disease progression. Nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD+), has emerged as a promising candidate for the treatment of age-related neurodegenerative disorders. NMN supplementation could restore NAD+ levels, thereby alleviating neuronal damage and slowing the progression of AD and other aging-associated diseases. AD is closely associated with autophagic impairment and oxidative stress. Our in vivo experiments demonstrated that NMN could ameliorate pathological and behavioral impairments in AD mice. Specifically, NMN enhanced autophagy and promoted p-tau clearance. Meanwhile, NMN could activate the Nrf2/Keap1/NQO1 pathway, thereby reducing the oxidative stress. Immunofluorescence results demonstrated that NMN could alleviate neuronal damage in AD mice. Furthermore, in vitro results showed that the p-tau clearance and antioxidant stress effects of NMN were suppressed by autophagy inhibitor, chloroquine (CQ) or bafilomycin A1 (BafA1), in Aß-induced PC12 cells. Lastly, when Nrf2 was knocked down, the antioxidant stress, autophagy enhancement, and p-tau clearance effects of NMN were all inhibited. In conclusion, our research indicates that NMN exerts therapeutic effect against AD by activating autophagy and the Nrf2/Keap1/NQO1 pathway through a mutual regulating mechanism of autophagy and antioxidative stress. These findings highlight the promising potential of NMN for the treatment of AD.

Association of the PCSK6 rs1531817(C/A) polymorphism with the prognosis and coronary stenosis in premature myocardial infarction patients: a prospective cohort study.

BACKGROUND: Proprotein convertase subtilisins/kexin 6 (PCSK6) polymorphisms have been shown to be associated with atherosclerosis progression. This research aimed to evaluate the relationship of PCSK6 rs1531817 polymorphisms with coronary stenosis and the prognosis in premature myocardial infarction (PMI) patients. METHODS: This prospective cohort analysis consecutively included 605 PMI patients who performed emergency percutaneous coronary intervention (PCI) at Tianjin Chest Hospital sequentially between January 2017 and August 2022, with major adverse cardiovascular events (MACEs) as the outcome. Analyses assessed the relationships among PCSK6 rs1531817 polymorphism, Gensini score (GS), triple vessel disease (TVD), and MACEs. RESULTS: 92 (16.8%) patients experienced MACEs with an average follow-up of 25.7 months. Logistic analysis revealed that the PCSK6 rs1531817 CA + AA genotype was an independent protective factor against high GS and TVD. Cox analysis revealed that the PCSK6 rs1531817 CA + AA genotype was an independent protective factor against MACEs. The mediation effect results showed that apolipoprotein A1/apolipoprotein B (ApoA1/ApoB) partially mediated the association between PCSK6 rs1531817 polymorphism and coronary stenosis and that total cholesterol/high-density lipoprotein (TC/HDL) and TVD partially and in parallel mediated the association between the PCSK6 rs1531817 polymorphism and MACEs. CONCLUSION: Patients with the PCSK6 CA + AA genotype have milder coronary stenosis and a better long-term prognosis; according to the mediation model, ApoA1/ApoB and TC/HDL partially mediate. These results may provide a new perspective on clinical therapeutic strategy for anti-atherosclerosis and improved prognosis in PMI patients.

Oxhide gelatin-regulated aramid nanofiber/liquid metal films with sandwiched structure for electromagnetic interference shielding.

Liquid metal (LM) based electromagnetic interference (EMI) shielding materials with high conductivity and continuous deformation capacity are important needs for meeting modern advanced electronic equipment. However, an independent free-standing film with LM is difficult to achieve due to its unique fluidity properties. Here, a simple alternating filtration film-forming method was utilized to orderly construct a sandwiched EMI shielding film with LM stabilized by bio-based oxhide gelatin (gel) as the intermediate conductive layer, and two films of aramid nanofibers/oxhide gel (ANF/gel) as the external insulating protective layers. This design not only prevents LM from being exposed to environmental conditions, but also reduces the risk of chemical corrosion in practical applications. Under optimal LM addition conditions, the sandwiched film (0.3-3 L) exhibited better EMI shielding performance of 50.4 dB in the X-band than the blended film (0.7 dB), as well as excellent mechanical properties (tensile strength of 65.8 MPa, strain 8.6 %). More importantly, the sandwiched film still maintained reliable EMI shielding performance after being experienced largely physical deformation. This study provides a new solution for preparing LM-based EMI shielding composites, and is expected to arouse pursuit of high EMI shielding effects of bio-based gel while also paying attention to their safety.

PLTS/ARAS-based financing risk resilience capability evaluation for fisheries enterprise: A case study of green transformation and upgrading.

Clearly delineating the key capabilities of organizational resilience for fisheries enterprises holds significant practical implications, as it can mitigate financing risks and foster the sustainable development of the fisheries industry. Based on the "dynamic capabilities perspective", this study constructs an analytical framework for the resilience capabilities of fisheries enterprises against financing risk. A hybrid method comprising the probabilistic linguistic term set, the decision-making trial and evaluation laboratory, and the additive ratio assessment is applied to a case study of Homey Group, examining the diverse pathways through which financing risk forms and impacts outcomes. The main findings are: (1) In the comprehensive assessment of the role of resilience capabilities in addressing the "Risk-Seeking-Decline Type" financing risk factors, market diversification and sustainable practices are accorded higher weights surpassing financial resources as the two most value-enhancing resilience capabilities. Enterprises characterized by a "Risk-Seeking-Loss Type" profile tend to assign higher weights to market diversification and technological infrastructure when evaluating financing risk resilience capabilities. (2) Regarding the key capabilities of organizational resilience, Homey Group possesses a weak risk management system for monitoring and evaluating significant risks and implementing control activities. (3) With regards to suggestions for improvement, it is advisable to delegate oversight of the risk identification process to a designated risk committee or specialists in risk management. The conclusions contribute to a deeper understanding of the nature and mechanism of resilience capabilities for fisheries enterprises and provides implications for risk management and sustainable development.

Magnetic compression anastomosis to restore biliary tract continuity after obstruction following major abdominal trauma: A case report.

BACKGROUND: The combination of magnetic compression anastomosis (MCA) and endoscopy has been used to treat biliary stricture after liver transplantation. However, its use for the treatment of complex biliary obstruction after major abdominal trauma has not been reported. This case report describes the successful use of MCA for the treatment of biliary obstruction resulting from major abdominal trauma. CASE SUMMARY: A 23-year-old man underwent major abdominal surgery (repair of liver rupture, right half colon resection, and ileostomy) following a car accident one year ago. The abdominal drainage tube, positioned at the Winslow foramen, was draining approximately 600-800 mL of bile per day. During the two endoscopic retrograde cholangiopancreatography procedures, the guide wire was unable to enter the common bile duct, which prevented placement of a biliary stent. MCA combined with endoscopy was used to successfully achieve magnetic anastomosis of the peritoneal sinus tract and duodenum, and then a choledochoduodenal stent was placed. Finally, the external biliary drainage tube was removed. The patient achieved internal biliary drainage leading to the removal of the external biliary drainage tube, which improved the quality of life. CONCLUSION: Magnetic compression technique can be used for the treatment of complex biliary obstruction with minimal operative trauma.

Novel magnetic compression technique for the treatment of postoperative anastomotic stenosis in rectal cancer: A case report.

BACKGROUND: The treatment of postoperative anastomotic stenosis after excision of rectal cancer is challenging. Endoscopic balloon dilation and radial incision are not effective in all patients. We present a new endoscopy-assisted magnetic compression technique (MCT) for the treatment of rectal anastomotic stenosis. We successfully applied this MCT to a patient who developed an anastomotic stricture after radical resection of rectal cancer. CASE SUMMARY: A 50-year-old man had undergone laparoscopic radical rectal cancer surgery at a local hospital 5 months ago. A colonoscopy performed 2 months ago indicated that the rectal anastomosis was narrow due to which ileostomy closure could not be performed. The patient came to the Magnetic Surgery Clinic of the First Affiliated Hospital of Xi'an Jiaotong University after learning that we had successfully treated patients with colorectal stenosis using MCT. We performed endoscopy-assisted magnetic compression surgery for rectal stenosis. The magnets were removed 16 d later. A follow-up colonoscopy performed after 4 months showed good anastomotic patency, following which, ileostomy closure surgery was performed. CONCLUSION: MCT is a simple, non-invasive technique for the treatment of anastomotic stricture after radical resection of rectal cancer. The technique can be widely used in clinical settings.

Modular and Regioselective Synthesis of Benzo-Fused Five-Membered Rings Enabled by Co/Ti Synergism.

The regiocontrol in constructing benzo-fused five-membered rings by C-H cyclization remains an important challenge. We report a highly general and regioselective methodology to access such heterocycles and indenones, where under the catalysis of CoBr2/bipyridine, aryl titanates, alkynes and EX2 (E = NR, S(O), RP(O), R2Si, CO, etc.) were assembled to various heterocycles and indenones in a modular manner. Unprecedented 1,2-Co/Ti heterobimetallic arylene and benzotitanole intermediates have played crucial roles in these syntheses.

The psychological side of menopause: evidence from the comorbidity network of menopausal, anxiety, and depressive symptoms.

OBJECTIVE: Numerous studies have uncovered a correlation between menopausal, anxiety, and depressive symptoms. How these symptoms interrelate and influence each other, however, remains unclear. This study aimed to identify the associations between menopausal, anxiety, and depressive symptoms using network analysis. METHODS: The participants comprised 423 women (Mage = 49.21 ± 4.01 y; range, 40-60 y) recruited from a menopause clinic at a tertiary hospital in Beijing, China. Demographic characteristics and menopausal, anxiety, and depressive symptoms were obtained through self-report questionnaires. Two networks were established: a partial correlation network and a Bayesian network. RESULTS: The menopausal symptom of nervousness exhibited a robust association with anxiety symptoms in both networks. Within the partial correlation network, the depressive symptom of tiredness emerged as a pivotal symptom, facilitating the co-occurrence of menopausal and depressive symptoms. Bayesian network analysis exhibited that the depressive symptom of a loss of interest was related to certain menopausal symptoms through depressive symptoms of tiredness and motor problems, both serving as critical links between menopausal symptoms and depression. Notably, four menopausal symptoms-arthralgia/myalgia, formication, sexual complaints, and urinary tract infection-appeared independent of other menopausal, anxiety, and depressive symptoms. CONCLUSIONS: Both psychological (eg, fatigue) and somatic (eg, hot flashes, headaches, and dizziness) menopausal symptoms demonstrate strong associations with depression. In providing optimal support for women's health during menopause, psychological interventions aimed at depression, particularly among those experiencing a loss of interest or pleasure in activities, should complement conventional therapies.

Constituents from Dendrobium aphyllum: Bibenzyls, furfurals, phenanthrenes, and phenylpropanoids and their antioxidant and anti-inflammatory potentials.

Chemical investigation on the aqueous extract of Dendrobium aphyllum led to the isolation of thirty-one constituents with structures identified by analysis of the extensive spectroscopic data (1D/2D NMR, MS, UV, and ECD), including previously undescribed two bibenzyls, one furfural, and one phenolic acid, namely trigonopol D (1), trigonopol C (2), dendrofunan A (10), and 6-(4-hydroxy-3-methoxyphenyl)-3,6-dioxohexyl acetate (30), respectively, as well as twenty-seven known ones. Among them, there were one new natural product (11), seven compounds (6-7, 9, 12, 20, 28, 31) described from the genus Dendrobium for the first time, and fifteen compounds (8, 13-17, 19, 21-27, 29) isolated from D. aphyllum for the first time. Further, the antioxidant and anti-inflammatory potentials of fifteen compounds (4-5, 8, 11-12, 14-19, 22, 24, 26, and 29) with significant scavenging capacities against DPPH and hydroxyl radicals, and virtual docking activities inhibiting COX-2 and 5-LOX, respectively. Our study may draw the attention of medicinal plant taxonomists and supply potential quality markers for discrimination of D. aphyllum from other species in Dendrobium genus.

Clypeasterol, a novel aromatic ergosterol skeleton from the mushroom Entoloma clypeatum.

Chemical investigation of the wild mushroom Entoloma clypeatum led to the isolation of one new A-nor B-aromatic C28 steroid (1), along with eight known compounds (2-9) from this mushroom. As far as we know, compound 1 represents an unprecedented type of natural product. The structure of the new compound was elucidated based on extensive spectroscopic data analysis of HR-ESI-MS, 1D, and 2D NMR, while the relative configuration was confirmed by NOESY correlations. In addition, the anti-inflammatory activity of compound 1 was evaluated against LPS induced NO production in RAW 264.7 macrophages. Compound 1 exhibited a moderate anti-inflammatory activity with an IC50 value of 24.56 ± 1.72 µM.

Microseismic comprehensive evaluation method for coal burst: a case study in the Zhaolou Coal Mine.

To explore the multiparameter precursor characteristics of pre- and post-coal burst. Based on a coal burst of LW 1305 in the Zhaolou Coal Mine, an early warning method combining stress‒strain curve and microseismic multiparameter is proposed. The research results show that coal burst was induced by the intrinsic static high-stress concentration and the strong external impact loading generated by fracturing of the key stratum. The precursors mainly characterize the enhancement trend of the S value, the sudden and sharp increase in the A(t) value, the continuous and abnormal decrease in the b value, the increasing absolute value of Z sharply and larger than 2, the continuous and abnormal decrease in the Qt value, and the dominant frequency moving to the low-frequency band. Essentially, many micro-fissures inside the key stratum initiated, converged and connected to form macro-fractures, which was verified by the attenuation rate of the K value. Considering the time-varying effect of the overlying stratum movement, the curves of the six parameters agree well with those of stress vs. strain, which indicates that it is reasonable to take the observed zone as a whole system to investigate the variation in the multiple parameters and fracturing of the key stratum. The research results can be applied to the monitoring, early warning and control of coal burst so that effective safety measures can be taken in real time.

C-terminal frameshift mutations generate viable knockout mutants with developmental defects for three essential protein kinases.

Loss-of-function mutants are fundamental resources for gene function studies. However, it is difficult to generate viable and heritable knockout mutants for essential genes. Here, we show that targeted editing of the C-terminal sequence of the embryo lethal gene MITOGEN-ACTIVATED PROTEIN KINASES 1 (OsMPK1) results in weak mutants. This C-terminal-edited osmpk1 mutants displayed severe developmental defects and altered disease resistance but generated tens of viable seeds that inherited the mutations. Using the same C-terminal editing approach, we also obtained viable mutants for a wall-associated protein kinase (Os07g0493200) and a leucine-rich repeat receptor-like protein kinase (Os01g0239700), while the null mutations of these genes were lethal. These data suggest that protein kinase activity could be reduced by introducing frameshift mutations adjacent to the C-terminus, which could generate valuable resources for gene function studies and tune protein kinase activity for signaling pathway engineering. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-024-00165-5.

Astaxanthin Rescues Memory Impairments in Rats with Vascular Dementia by Protecting Against Neuronal Death in the Hippocampus.

Vascular dementia (VaD) is a cognitive disorder characterized by a decline in cognitive function resulting from cerebrovascular disease. The hippocampus is particularly susceptible to ischemic insults, leading to memory deficits in VaD. Astaxanthin (AST) has shown potential therapeutic effects in neurodegenerative diseases. However, the mechanisms underlying its protective effects in VaD and against hippocampal neuronal death remain unclear. In this study, We used the bilateral common carotid artery occlusion (BCCAO) method to establish a chronic cerebral hypoperfusion (CCH) rat model of VaD and administered a gastric infusion of AST at 25 mg/kg per day for 4 weeks to explore its therapeutic effects. Memory impairments were assessed using Y-maze and Morris water maze tests. We also performed biochemical analyses to evaluate levels of hippocampal neuronal death and apoptosis-related proteins, as well as the impact of astaxanthin on the PI3K/Akt/mTOR pathway and oxidative stress. Our results demonstrated that AST significantly rescued memory impairments in VaD rats. Furthermore, astaxanthin treatment protected against hippocampal neuronal death and attenuated apoptosis. We also observed that AST modulated the PI3K/Akt/mTOR pathway, suggesting its involvement in promoting neuronal survival and synaptic plasticity. Additionally, AST exhibited antioxidant properties, mitigating oxidative stress in the hippocampus. These findings provide valuable insights into the potential therapeutic effects of AST in VaD. By elucidating the mechanisms underlying the actions of AST, this study highlights the importance of protecting hippocampal neurons and suggests potential targets for intervention in VaD. There are still some unanswered questions include long-term effects and optimal dosage of the use in human. Further research is warranted to fully understand the therapeutic potential of AST and its application in the clinical treatment of VaD.

Molecular Characteristics of Salmonella Spp. Responsible for Bloodstream Infections in a Tertiary Hospital in Nanjing, China, 2019-2021.

Objective: To investigate the clinical and molecular characteristics of Salmonella spp. causing bloodstream infections (BSIs) in our hospital. Methods: We studied 22 clinical Salmonella isolates from BSIs and 16 from non-BSIs, performing antimicrobial susceptibility testing (AST) and whole genome sequencing (WGS). The analysis included serovars, antibiotic resistance genes (ARGs), virulence factors (VFs), sequence types (STs), plasmid replicons, and genetic relationships. We also assessed pathogenicity of the isolates causing BSIs through growth, biofilm formation, and anti-serum killing assays. Results: WGS analysis identified 13 Salmonella serovars, with four responsible for BSIs. S. Enteritidis was the most prevalent serovar, involved in 19 (50.0%) cases. BSIs were caused by 17S. Enteritidis, two S. Typhimurium, two S. Munster and one S. Diguel. Of the 38 isolates, 27 (71.1%) exhibited high resistance to ampicillin, and 24 (63.2%) to ampicillin/sulbactam. Thirty-six types of ARGs were identified, with blaTEM-1B (n = 25, 65.8%) being the most frequent. Ten plasmid replicons were found; the combination of IncFIB(S)-IncFII(S)-IncX1 was the most common in S. Enteritidis (94.7%). Fifteen STs were identified, among which ST11 was the most prevalent and clonally disseminated, primarily responsible for BSIs. A total of 333 different VFs were detected, 177 of which were common across all strains. No significant differences were observed between the BSI and non-BSI isolates in terms of resistance rates, ARGs, plasmid replicons, and VFs, except for seven VFs. No strong pathogenicity was observed in the BSI-causing isolates. Conclusion: BSIs were predominantly caused by clonally disseminated S. Enteritidis ST11, the majority of which carried multiple ARGs, VFs and plasmid replicons. This study provides the first data on clonally disseminated S. Enteritidis ST11 causing BSIs, highlighting the urgent need for enhanced infection control measures.

Synthesis of Multisubstituted 2,3-Allenamides via Palladium-Catalyzed Carbonylation of Propargylic Esters.

2,3-Allenamides are an important class of unsaturated group-substituted carbonyl compounds. A palladium-catalyzed aminocarbonylation of propargyl acetates with amines for the synthesized tri-/tetrasubstituted 2,3-allenamides has been developed. A broad range of tri-/tetrasubstituted 2,3-allenamides have been prepared from propargyl acetates in good to excellent yields. The reaction featured mild reaction conditions and good functional group tolerance. The applicability of this methodology was further highlighted by the late-stage modification of several natural products and pharmaceuticals.