Transcriptomic Landscape Analysis Reveals a Persistent DNA Damage Response in Metabolic Dysfunction-associated Steatohepatitis Post-dietary Intervention.

Background and Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) and its more advanced form, metabolic dysfunction-associated steatohepatitis, have emerged as the most prevalent liver diseases worldwide. Currently, lifestyle modification is the foremost guideline-recommended management strategy for MASLD. However, it remains unclear which detrimental signals persist in MASLD even after disease remission. Thus, we aimed to examine the persistent changes in liver transcriptomic profiles following this reversal. Methods: Male C57BL/6J mice were divided into three groups: Western diet (WD) feeding, chow diet (CD) feeding, or diet reversal from WD to CD. After 16 weeks of feeding, RNA sequencing was performed on the mice's livers to identify persistent alterations characteristic of MASLD. Additionally, RNA sequencing databases containing high-fat diet-fed P53-knockout mice and human MASLD samples were utilized. Results: WD-induced MASLD triggered persistent activation of the DNA damage response (DDR) and its primary transcription factor, P53, long after the resolution of the hepatic phenotype through dietary reversal. Elevated levels of P53 might promote apoptosis, thereby exacerbating metabolic dysfunction-associated steatohepatitis, as they strongly correlated with hepatocyte ballooning, an indicator of apoptosis activation. Moreover, P53 knockout in mice led to downregulated expression of apoptosis signaling in the liver. Mechanistically, P53 may regulate apoptosis by transcriptionally activating the expression of apoptosis-enhancing nuclease (AEN). Consistently, P53, AEN, and the apoptosis process all exhibited persistently elevated expression and showed a strong inter-correlation in the liver following dietary reversal. Conclusions: The liver demonstrated upregulation of DDR signaling and the P53-AEN-apoptosis axis both during and after exposure to WD. Our findings provide new insights into the mechanisms of MASLD relapse, highlighting DDR signaling as a promising target to prevent MASLD recurrence.

Convergent and Stereospecific Synthesis of Highly Substituted Azepines.

This study reported a convergent pattern to stereospecifically synthesize 4,5-dihydrogen azepine from simple and readily available starting materials, addressing synthetic and stereoselective issues. Several synthetically important transformations, such as Simmon-Smith cyclopropanation, halogenation, and hydrogenation, demonstrated the utilities of this strategy. Particularly, the final azepine products could effectively contract into highly substituted pyridine derivatives through an intramolecular oxidation rearrangement.

Association Between Systolic Blood Pressure and in-Hospital Mortality Among Congestive Heart Failure Patients with Chronic Obstructive Pulmonary Disease in the Intensive Care Unit: A Retrospective Cohort Study.

Background: There has been a growing body of research focusing on patients with Congestive Heart Failure (CHF) and chronic obstructive pulmonary disease (COPD) admitted to the intensive care unit (ICU). However, the optimal blood pressure (BP) level for such patients remains insufficiently explored. This study aimed to investigate the associations between systolic blood pressure (SBP) and in-hospital mortality among ICU patients with both CHF and COPD. Methods: This retrospective cohort study enrolled 6309 patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. SBP was examined as both a continuous and categorical variable, with the primary outcome being in-hospital mortality. The investigation involved multivariable logistic regression, restricted cubic spline regression, and subgroup analysis to determine the relationship between SBP and mortality. Results: The cohort consisted of 6309 patients with concurrent CHF and COPD (3246 females and 3063 males), with an average age of 73.0 ± 12.5 years. The multivariate analysis revealed an inverse association between SBP and in-hospital mortality, both as a continuous variable (odds ratio = 0.99 [95% CI, 0.99~1]) and as a categorical variable (divided into quintiles). Restricted cubic spline analysis demonstrated an L-shaped relationship between SBP and mortality risk (P nonlinearity < 0.001), with an inflection point at 99.479 mmHg. Stratified analyses further supported the robustness of this correlation. Conclusion: The relationship between SBP and in-hospital mortality in patients with both CHF and COPD follows an L-shaped pattern, with an inflection point at approximately 99.479 mmHg.

NLRP1 inhibits lung adenocarcinoma growth through mediating mitochondrial dysregulation in an inflammasome-independent manner.

NLRP1, the first identified inflammasome-forming sensor, is thought to be involved in cancer, yet its definite function in lung adenocarcinoma (LUAD) remains unclear. Herein, we explored the expression and function of NLRP1 in LUAD. Decreased NLRP1 expression was identified in LUAD, which was associated with a poor prognosis. Overexpression of NLRP1 inhibited tumor growth in vitro and in vivo. Mechanically, this effect was observed regardless of inflammasome activation. Further studies revealed that overexpression of NLRP1 downregulated the phosphorylation of DRP1 and promoted mitochondrial fusion, which was mediated by inhibition of NF-κB activity. NF-κB agonist could neutralize the effect of NLRP1 on mitochondrial dynamics. In addition, LUAD sensitivity to cisplatin was enhanced by decreased mitochondrial fission resulting from up-regulated NLRP1. In conclusion, our findings demonstrated an unexpected role of NLRP1 in LUAD by modulating mitochondrial activities, which provides strong evidence for its potential in LUAD treatment.

Insight into the therapeutic effects of artesunate in relieving metabolic-associated steatohepatitis from transcriptomic and lipidomics analyses.

OBJECTIVES: Artesunate (ART) is a water-soluble derivative of artemisinin, which has shown anti-inflammatory, anti-tumor, and immunomodulating effects. We aimed to investigate the potential therapeutic effects and mechanisms of ART in metabolic dysfunction-associated steatohepatitis (MASH). METHODS: The mice were randomly divided into the control group, high-fat, high-cholesterol diet-induced MASH group, and the MASH treated with ART (30 mg/kg once daily) group. Liver enzymes, lipids, and histological features were compared among groups. The molecular mechanisms were studied by transcriptomic and lipidomics analyses of liver tissues. RESULTS: The mice of the MASH group had significantly increased hepatic fat deposition and inflammation in terms of biochemical indicators and pathological manifestations than the control group. The ART-treated group had improved plasma liver enzymes and hepatic cholesterol, especially at week 4 of intervention (p < 0.05). A total of 513 differentially expressed genes and 59 differentially expressed lipids were identified in the MASH group and the MASH+ART group. Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment test showed that ART regulated glycerolipid metabolism pathway and enhanced fatty acid degradation. Peroxisome proliferator-activated receptor (PPAR)-α acted as a key transcription factor in the treatment of MASH with ART, which was confirmed by cell experiment. CONCLUSIONS: ART significantly improved fat deposition and inflammatory manifestations in MASH mice, with potential therapeutic effects. The mechanism of artemisinin treatment for MASH may involve extensive regulation of downstream genes by upstream transcription factors, such as PPAR-α, to restore hepatic lipid homeostasis.

[Current Situation and Influencing Factors of Caregivers' Pressuring Feeding Style in Infants of 6-11 Months Old in Rural Areas of Sichuan Province].

Objective To investigate the status and influencing factors of pressuring feeding style among caregivers in remote rural areas of Sichuan province. Methods Multistage sampling was conducted to select infants of 6-11 months old who had received complementary food and their caregivers in remote rural areas of Sichuan province.A questionnaire was used to collect sociodemographic characteristics of infants and their caregivers,pressuring feeding behaviors,feeding environment,and caregivers' negative emotions.Quantile regression was employed to analyze the factors influencing pressuring feeding among caregivers of infants. Results A total of 1358 pairs of infants and their caregivers were included,with the pressuring feeding behavior score of 11 (8,14).Parity was the protective factor for caregivers' pressuring feeding (ß25=-1.17,P<0.001;ß50=-1.40,P=0.002;ß75=-2.18,P<0.001).Whether infants played with toys while eating (ß25=1.00,P<0.001;ß50=1.20,P=0.003;ß75=1.42,P<0.001) and whether infants watched TV/mobile phones (ß25=0.50,P=0.048;ß50=1.07,P=0.004) were the risk factors.At the 75th percentile,caregivers' negative emotions were the risk factor for pressuring feeding (ß75=0.94,P=0.015).Caregivers' education background (ß25=0.83,P=0.034;ß50=0.87,P=0.021) and family income (ß75=1.09,P=0.012) were also significantly associated with pressuring feeding scores at different quartile points. Conclusion Pressuring feeding behaviors of caregivers in remote rural areas of Sichuan province need to be improved.Based on the characteristics of infants and their families,guidance should be carried out to improve the feeding environment and the mental health of caregivers,thereby promoting reasonable feeding behaviors among caregivers of infants in rural areas.

Tailoring near-infrared amyloid-ß probes with high-affinity and low background based on CN and amphipathic regulatory strategies and in vivo imaging of AD mice.

Amyloid-ß (Aß) species (Aß fibrils and Aß plaques), as one of the typical pathological markers of Alzheimer's disease (AD), plays a crucial role in AD diagnosis. Currently, some near-infrared I (NIR I) Aß probes have been reported in AD diagnosis. However, they still face challenges such as strong background interference and the lack of effective probe design. In this study, we propose molecular design strategy that incorporates CN group and amphiphilic modulation to synthesize a series of amphiphilic NIR I Aß probes, surpassing the commercial probe ThT and ThS. Theoretical calculations indicate that these probes exhibit stronger interaction with amino acid residues in the cavities of Aß. Notably, the probes containing CN group display the ability of binding two distinct sites of Aß, which dramatically enhanced the affinity to Aß species. Furthermore, these probes exhibit minimal fluorescence in aqueous solution and offer ultra-high signal-to-noise ratio (SNR) for in vitro labeling, even in wash-free samples. Finally, the optimal probe DM-V2CN-PYC3 was utilized for in vivo imaging of AD mice, demonstrating its rapid penetration through the blood-brain barrier and labelling to Aß species. Moreover, it enabled long-term monitoring for a duration of 120 min. These results highlight the enhanced affinity and superior performance of the designed NIR I Aß probe for AD diagnosis. The molecular design strategy of CN and amphiphilic modulation presents a promising avenue for the development Aß probes with low background in vivo/in vitro imaging for Aß species.

Interactions at the Oviposition Scar: Molecular and Metabolic Insights into Elaeagnus angustifolia's Resistance Response to Anoplophora glabripennis.

The Russian olive (Elaeagnus angustifolia), which functions as a "dead-end trap tree" for the Asian long-horned beetle (Anoplophora glabripennis) in mixed plantations, can successfully attract Asian long-horned beetles for oviposition and subsequently kill the eggs by gum. This study aimed to investigate gum secretion differences by comparing molecular and metabolic features across three conditions-an oviposition scar, a mechanical scar, and a healthy branch-using high-performance liquid chromatography and high-throughput RNA sequencing methods. Our findings indicated that the gum mass secreted by an oviposition scar was 1.65 times greater than that secreted by a mechanical scar. Significant differences in gene expression and metabolism were observed among the three comparison groups. A Kyoto Encyclopedia of Genes and Genomes annotation and enrichment analysis showed that an oviposition scar significantly affected starch and sucrose metabolism, leading to the discovery of 52 differentially expressed genes and 7 differentially accumulated metabolites. A network interaction analysis of differentially expressed metabolites and genes showed that EaSUS1, EaYfcE1, and EaPGM1 regulate sucrose, uridine diphosphate glucose, α-D-glucose-1P, and D-glucose-6P. Although the polysaccharide content in the OSs was 2.22 times higher than that in the MSs, the sucrose content was lower. The results indicated that the Asian long-horned beetle causes Russian olive sucrose degradation and D-glucose-6P formation. Therefore, we hypothesized that damage caused by the Asian long-horned beetle could enhance tree gum secretions through hydrolyzed sucrose and stimulate the Russian olive's specific immune response. Our study focused on the first pair of a dead-end trap tree and an invasive borer pest in forestry, potentially offering valuable insights into the ecological self-regulation of Asian long-horned beetle outbreaks.

Copper-Catalyzed Nucleophilic Cycloisomerization Cascade Constructing Azepinoindolizine.

Numerous effective bioisosteric replacements have been identified through substituting scaffolds and functional groups in lead molecules with alternative ones that preserve or enhance the desired biological activity of the original compound. Here, a copper-catalyzed nucleophilic cycloisomerization was developed to access potential bioisosteric replacements of azepinoindole. In this process, "tetra-alkene" characteristic of indolizine undergoes a 12π electrocyclization, offering a complementary method to obtain azepinoindolizine derivatives that are otherwise challenging to prepare through conventional means.

Unraveling the Roles of Ionic Size and Hydrogen Bonding in Electric Field-Driven Ion Emission from Hydroxylamine Nitrate-Based Ionic Liquids.

Ionic size and hydrogen bonding (HB) may play significant roles in controlling ion emission from HAN (hydroxylamine nitrate)-based ionic liquids (ILs) but have received little attention. In this paper, the ion emission behavior and mechanism in an external electric field are meticulously investigated using the molecular dynamics (MD) method and density functional theory. We find that the higher the proportion of ionic HAN in the blend of ILs, the longer the delay time of the ion start-up emission. In the positive mode, cations can evaporate directly from the surface of the studied ILs and manifest exclusively as the [EMIM]+ monomers within the simulation time scale, whereas in the negative mode, a variety of complicated anion clusters are emitted. As a result, the average charge-to-mass ratio of the positively charged species remarkably exceeds that of the negatively charged species. This large difference is attributed to the relatively larger size of the [EMIM]+ ion and the absence of substantial HB interactions between the [EMIM]+ ion and any other monomer, leading to diminished binding energies. Conversely, the strong HB interactions, primarily constituted by N-H--O and O-H--O hydrogen bonds, are clearly found in the [EtSO4]--based and HAN-based clusters. In addition, the [NO3]- and [EtSO4]- ions tend to combine with the small-sized [HA]+ ions to form large anion clusters rather than with the [EMIM]+ ions. The energy decomposition results further elucidate that the orbital interaction plays a pivotal role in the [NO3]- and [EtSO4]--based clusters. The findings clearly elucidate the experimental phenomena observed in previous studies and have implications for the formulation of multimode IL propellants.

FMD-UNet: fine-grained feature squeeze and multiscale cascade dilated semantic aggregation dual-decoder UNet for COVID-19 lung infection segmentation from CT images.

With the advancement of computer-aided diagnosis, the automatic segmentation of COVID-19 infection areas holds great promise for assisting in the timely diagnosis and recovery of patients in clinical practice. Currently, methods relying on U-Net face challenges in effectively utilizing fine-grained semantic information from input images and bridging the semantic gap between the encoder and decoder. To address these issues, we propose an FMD-UNet dual-decoder U-Net network for COVID-19 infection segmentation, which integrates a Fine-grained Feature Squeezing (FGFS) decoder and a Multi-scale Dilated Semantic Aggregation (MDSA) decoder. The FGFS decoder produces fine feature maps through the compression of fine-grained features and a weighted attention mechanism, guiding the model to capture detailed semantic information. The MDSA decoder consists of three hierarchical MDSA modules designed for different stages of input information. These modules progressively fuse different scales of dilated convolutions to process the shallow and deep semantic information from the encoder, and use the extracted feature information to bridge the semantic gaps at various stages, this design captures extensive contextual information while decoding and predicting segmentation, thereby suppressing the increase in model parameters. To better validate the robustness and generalizability of the FMD-UNet, we conducted comprehensive performance evaluations and ablation experiments on three public datasets, and achieved leading Dice Similarity Coefficient (DSC) scores of 84.76, 78.56 and 61.99% in COVID-19 infection segmentation, respectively. Compared to previous methods, the FMD-UNet has fewer parameters and shorter inference time, which also demonstrates its competitiveness.

DNAJA1 regulates protein ubiquitination and is essential for spermatogenesis in the testes of mice and rats.

DNAJA1 is a member of type I DnaJ proteins, which is essential for spermatogenesis and male fertility. However, its expression pattern in the testes and its impact on spermatogenesis remains unclear. Our study aimed to elucidate the mechanism of action of DNAJA1. We employed DNAJA1 knockout mice in this study. Western blotting and immunofluorescence analysis were conducted to determine the protein abundance of DNAJA1 in testes at various developmental stages. Our results revealed that DNAJA1 is predominantly expressed in the testes, and its knockout leads to complete infertility in male mice. We observed that DNAJA1 protein levels increased on postnatal days 14, 21, and 28, peaking on postnatal day 35 in mice. Immunofluorescence staining indicated that DNAJA1 expression varies across different stages of the spermatogenesis cycle. Additionally, DNAJA1 was absent in epididymal sperm. In early- and mid-stage tubules, DNAJA1 protein distribution was co-localized with residual bodies in elongating spermatids. Furthermore, we found that DNAJA1 knockout significantly reduced protein polyubiquitination in the testis. Analysis of the GEO database showed that DNAJA1 levels were significantly decreased in semen samples from subjects with teratozoospermia, asthenozoospermia, and impaired spermatogenesis. Our findings suggest that DNAJA1 is an essential protein for spermatogenesis, and its deletion reduces protein polyubiquitination in the testis, ultimately resulting in infertility and spermatogenesis defects.

[Microplastic Characteristics and Risk Assessment in Multigate Dam-type River].

Microplastics pose a serious ecological threat to rivers in China, and the construction of a large number of dams has complicated this problem. Ten dams of the Shaying River were chosen to investigate the abundance and composition of microplastics in surface water and sediments of the reservoir and upstream river. Ecological risk was evaluated using species sensitive distribution （SSD） and pollution load index （PLI）. The results showed that the Shaying River was exposed to a severe risk of microplastics from upstream to downstream. The construction of dams did not significantly affect the distribution of microplastics in the river. River sediments became a sink for microplastics in the surface water； however, the ecological risk posed by microplastics in the surface water was greater, and the comparison of the two assessment methods showed that the species sensitivity distribution assessment better reflected the accumulation and feeding behavior of organisms to pollutants compared to the pollution load index.

Rotavirus outbreaks in China, 1982-2021: a systematic review.

Background: Rotavirus is globally recognized as an important cause of acute gastroenteritis in young children. Whereas previous studies focused more on sporadic diarrhea, the epidemiological characteristics of rotavirus outbreaks have not been systematically understood. Methods: This systematic review was carried out according to the Preferred Reporting Items for Systematic Review and Meta-Analysis standards, WANFANG, China National Knowledge Infrastructure (CNKI), PubMed, and Web of Science databases were searched from database inception to February 20, 2022. We used SPSS 21.0 statistical software for data analysis, RStudio1.4.1717, and ArcGIS trial version for plotting bar graphs and maps. Results: Among 1,596 articles, 78 were included, with 92 rotavirus outbreaks and 96,128 cases. Most outbreaks (67.39%, 62/92) occurred in winter and spring. The number of rotavirus outbreaks reported in the eastern region was more than that in the western region. Outbreaks were most commonly reported in villages (33/92, 35.87%), followed by hospitals (19, 20.65%). The outbreak duration was longer in factories and workers' living places, and villages, while it was shorter in hospitals. Waterborne transmission was the main transmission mode, with the longest duration and the largest number of cases. Rotavirus groups were identified in 66 outbreaks, with 40 outbreaks (60.61%) caused by Group B rotaviruses and 26 outbreaks (39.39%) caused by Group A rotaviruses. Significant differences were found in duration, number of cases, settings, population distribution, and transmission modes between Groups A and B rotavirus outbreaks. Conclusion: Rotavirus is an important cause of acute gastroenteritis outbreaks in China. It should also be considered in the investigation of acute gastroenteritis outbreaks, especially norovirus-negative outbreaks.

Anti-inflammatory and DNA Repair Effects of Astragaloside IV on PC12 Cells Damaged by Lipopolysaccharide.

OBJECTIVE: This study aimed to establish a neural cell injury model in vitro by stimulating PC12 cells with lipopolysaccharide (LPS) and to examine the effects of astragaloside IV on key targets using high-throughput sequence technology and bioinformatics analyses. METHODS: PC12 cells in the logarithmic growth phase were treated with LPS at final concentrations of 0.25, 0.5, 0.75, 1, and 1.25 mg/mL for 24 h. Cell morphology was evaluated, and cell survival rates were calculated. A neurocyte inflammatory model was established with LPS treatment, which reached a 50% cell survival rate. PC12 cells were treated with 0.01, 0.1, 1, 10, or 100 µmol/L astragaloside IV for 24 h. The concentration of astragaloside IV that did not affect the cell survival rate was selected as the treatment group for subsequent experiments. NOS activity was detected by colorimetry; the expression levels of ERCC2, XRCC4, XRCC2, TNF-α, IL-1ß, TLR4, NOS and COX-2 mRNA and protein were detected by RT-qPCR and Western blotting. The differentially expressed genes (DEGs) between the groups were screened using a second-generation sequence (fold change>2, P<0.05) with the following KEGG enrichment analysis, RT-qPCR and Western blotting were used to detect the mRNA and protein expression of DEGs related to the IL-17 pathway in different groups of PC12 cells. RESULTS: The viability of PC12 cells was not altered by treatment with 0.01, 0.1, or 1 µmol/L astragaloside IV for 24 h (P>0.05). However, after treatment with 0.5, 0.75, 1, or 1.25 mg/mL LPS for 24 h, the viability steadily decreased (P<0.01). The mRNA and protein expression levels of ERCC2, XRCC4, XRCC2, TNF-α, IL-1ß, TLR4, NOS, and COX-2 were significantly increased after PC12 cells were treated with 1 mg/mL LPS for 24 h (P<0.01); however, these changes were reversed when PC12 cells were pretreated with 0.01, 0.1, or 1 µmol/L astragaloside IV in PC12 cells and then treated with 1 mg/mL LPS for 24 h (P<0.05). Second-generation sequencing revealed that 1026 genes were upregulated, while 1287 genes were downregulated. The DEGs were associated with autophagy, TNF-α, interleukin-17, MAPK, P53, Toll-like receptor, and NOD-like receptor signaling pathways. Furthermore, PC12 cells treated with a 1 mg/mL LPS for 24 h exhibited increased mRNA and protein expression of CCL2, CCL11, CCL7, MMP3, and MMP10, which are associated with the IL-17 pathway. RT-qPCR and Western blotting analyses confirmed that the DEGs listed above corresponded to the sequence assay results. CONCLUSION: LPS can damage PC12 cells and cause inflammatory reactions in nerve cells and DNA damage. astragaloside IV plays an anti-inflammatory and DNA damage protective role and inhibits the IL-17 signaling pathway to exert a neuroprotective effect in vitro.

Liquid-Phase Exfoliation of 3D Metal-Organic Frameworks into Nanosheets.

Traditionally, the acquisition of 2D materials involved the exfoliation of layered crystals. However, the anisotropic bonding arrangements within 3D crystals indicate they are mechanically reminiscent of 2D counterparts and could also be exfoliated into nanosheets. This report delineates the preparation of 2D nanosheets from six representative 3D metal-organic frameworks (MOFs) through liquid-phase exfoliation. Notably, the cleavage planes of exfoliated nanosheets align perpendicular to the direction of the minimum elastic modulus (Emin) within the pristine 3D frameworks. The findings suggest that the in-plane and out-of-plane bonding forces of the exfoliated nanosheets can be correlated with the maximum elastic modulus (Emax) and Emin of the 3D frameworks, respectively. Emax influences the ease of cleaving adjacent layers, while Emin governs the ability to resist cracking of layers. Hence, a combination of large Emax and small Emin indicates an efficient exfoliation process, and vice versa. The ratio of Emax/Emin, denoted as Amax/min, is adopted as a universal index to quantify the ease of mechanical exfoliation for 3D MOFs. This ratio, readily accessible through mechanical experiments and computation, serves as a valuable metric for selecting appropriate exfoliation methods to produce surfactant-free 2D nanosheets from various 3D materials.

Type 2 herpes simplex virus-induced anti-N-methyl-D-aspartate receptor encephalitis responsive to immunoglobulin monotherapy.

Herpes simplex virus-2 encephalitis (HSV2E) in immunocompetent adults is exceptionally rare, and the subsequent onset of autoimmune encephalitis after HSV2E is even less common. This report presents the inaugural Chinese case of anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) induced by HSV2E, confirmed via metagenomic next-generation sequencing (mNGS). The patient demonstrated a favorable response to intravenous immunoglobulin (IVIG) monotherapy. This case emphasizes the importance of considering autoimmune encephalitis in patients exhibiting new or recurrent neurological symptoms after HSV2E recovery. Comprehensive mNGS and neuronal antibody testing are essential for timely diagnosis. Moreover, IVIG monotherapy can serve as an effective treatment for NMDARE induced by HSV2, providing a viable alternative, particularly when steroid therapy is contraindicated.

Prevalence and Genomic Characterization of Multidrug-Resistant Salmonella enterica Serovar Kentucky Sequence Type 198 Circulating - Beijing Municipality, China, 2016-2023.

Introduction: Highly fluoroquinolone-resistant Salmonella enterica serovar Kentucky (S. Kentucky) of sequence type (ST) 198 has emerged as a global multidrug-resistant (MDR) clone, posing a threat to public health. Methods: Whole genome sequencing and antibiotic susceptibility testing was used to characterize the population structure and evolutionary history of 54 S. Kentucky isolates recovered from food and human clinical cases in Beijing from 2016 to 2023. Results: All 54 S. Kentucky ST198 isolates exhibited resistance to quinolones, carrying point mutations in the quinolone resistance-determining regions (gyrA_S83F and parC_S80I). Resistance to other antibiotics (folate pathway inhibitors, cephems, aminoglycosides, phenicols, rifamycin, fosfomycin, macrolides, and tetracyclines), mediated by the sul1, sul2, dfrA14, bla CTX-M, bla TEM-1B, aac(3)-Id, aadA2, aadA7, aph(3')-I, aph(3'')-Ib, rmtB, floR, arr-2, fosA, mph(A), and tet(A) genes, was also observed in different combinations. The Beijing S. Kentucky ST198 evolutionary tree was divided into clades 198.2-1 and 198.2-2, which were further differentiated into three subclades: 198.2-2A, 198.2-2B, and 198.2-2C. Compared with the extended-spectrum ß-lactamase-encoding gene bla CTX-M-14b in 198.2-1, the co-existence of bla CTX-M-55 and bla TEM-1B, as well as chromosomally located qnrS1, was detected in most 198.2-2 isolates, which showed more complex MDR phenotypes. S. Kentucky ST198 outbreak isolates derived from two predominant clonal sources: 198.2-1 with cgST236434 and 198.2-2A with cgST296405. Conclusions: The S. Kentucky population in Beijing is genetically diverse, consisting of multiple co-circulating lineages that have persisted since 2016. Strengthening surveillance of food and humans will aid in implementing measures to prevent and control the spread of AMR.

Effects of Hypertension on Alzheimer's Disease: Updates in Pathophysiological and Neuroimaging Findings.

Alzheimer's disease (AD) is recognized as the leading cause of dementia, imposing a significant economic toll on society. Despite the emergence of novel therapeutic approaches for AD, their efficacy and safety mandates further validation through rigorous clinical trials. In this context, hypertension (HTN) has garnered considerable attention as an amendable risk factor for AD. Research indicates that hypertension during midlife is associated with an elevated risk of AD in later years, influencing both the onset and progression of the disease. Nevertheless, the relationship between AD and hypertension in the later stages of life remains a subject of debate. Moreover, the consequences of blood pressure reduction on cognitive function, along with the optimal pharmacological interventions and therapeutic thresholds for hypertension, have emerged as pivotal areas of inquiry. This review synthesizes findings on epidemiology, neuroimaging, and biomarkers, and the effects of antihypertensive medications to elucidate the link between hypertension and cognitive performance. We particularly investigate how hypertension and AD are related by plasma sulfide dysregulation, offering possible indicators for future diagnosis and therapy.