Comparison of Mixed Reality-Assisted Spinal Puncture with Landmark-Guided Spinal Puncture by Novice Practitioners: A Pilot Study.

Background: Performing spinal anaesthesia in elderly patients with ligament calcification or hyperostosis is challenging for novice practitioners. This pilot study aimed to compare the effectiveness of mixed reality-assisted spinal puncture (MRasp) with that of landmark-guided spinal puncture (LGsp) by novice practitioners in elderly patients. Methods: In this pilot study, 36 patients (aged ≥65 years) scheduled for elective surgery under spinal anaesthesia by anaesthesiology residents were included. Patients were randomly assigned to the MRasp group (n = 18) or the LGsp group (n = 18). The outcomes included the number of needle insertion attempts, redirection attempts, passes, the rate of successful first-attempt needle insertion, the rate of successful first needle pass, the spinal puncture time, the total procedure time, and the incidence of perioperative complications. Results: The median number of needle insertion attempts was significantly fewer in the MRasp group than in the LGsp group (1.0 vs 2.0, P = 0.023). The proportion of patients with successful first-attempt needle insertion was 72.2% in the MRasp group and 44.4% in the LGsp group (P = 0.176). The incidence of perioperative complications did not significantly differ between the two groups. Conclusion: This pilot study found that novice practitioners made significantly fewer needle insertion attempts in the MRasp group compared to the LGsp group when performing spinal anaesthesia on elderly patients. A future randomized controlled trial (RCT) is warranted to validate its effectiveness. Trial Registration: This trial was registered at https://www.chictr.org.cn/showproj.html?proj=178960 (ChiCTR-IPR-2300068520). Public title: Mixed reality-assisted versus landmark-guided spinal puncture in elderly patients: a randomized controlled pilot study. Principal investigator: Lei Gao. The registration date was February 22, 2023. The date of the first participant enrolment was February 27, 2023.

We developed virtual spine-presenting technology and patented optimal trajectory design technology to assist in spinal puncture and reported that the median number of needle insertion attempts was significantly fewer in the mixed reality-assisted spinal puncture group than in the landmark-guided spinal puncture group.

Adaptive evolution of carbapenem-resistant hypervirulent Klebsiella pneumoniae in the urinary tract of a single patient.

The emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) is a growing concern due to its high mortality and limited treatment options. Although hypermucoviscosity is crucial for CR-hvKp infection, the role of changes in bacterial mucoviscosity in the host colonization and persistence of CR-hvKp is not clearly defined. Herein, we observed a phenotypic switch of CR-hvKp from a hypermucoviscous to a hypomucoviscous state in a patient with scrotal abscess and urinary tract infection (UTI). This switch was attributed to decreased expression of rmpADC, the regulator of mucoid phenotype, caused by deletion of the upstream insertion sequence ISKpn26. Postswitching, the hypomucoid variant showed a 9.0-fold decrease in mice sepsis mortality, a >170.0-fold reduction in the ability to evade macrophage phagocytosis in vitro, and an 11.2- to 40.9-fold drop in growth rate in normal mouse serum. Conversely, it exhibited an increased residence time in the mouse urinary tract (21 vs. 6 d), as well as a 216.4-fold boost in adhesion to bladder epithelial cells and a 48.7% enhancement in biofilm production. Notably, the CR-hvKp mucoid switch was reproduced in an antibiotic-free mouse UTI model. The in vivo generation of hypomucoid variants was primarily associated with defective or low expression of rmpADC or capsule synthesis gene wcaJ, mediated by ISKpn26 insertion/deletion or base-pair insertion. The spontaneous hypomucoid variants also outcompeted hypermucoid bacteria in the mouse urinary tract. Collectively, the ISKpn26-associated mucoid switch in CR-hvKp signifies the antibiotic-independent host adaptive evolution, providing insights into the role of mucoid switch in the persistence of CR-hvKp.

Burden of Child Anemia Attributable to Fine Particulate Matters Brought by Sand Dusts in Low- and Middle-Income Countries.

Addressing environmental factors has recently been recommended to curb the growing trend of anemia in low- and middle-income countries (LMICs). Fine particulate matter (PM2.5) generated by dust storms were concentrated in place with a high prevalence of anemia. In a multicounty, multicenter study, we analyzed the association between anemia and life-course averaged exposure to dust PM2.5 among children aged <5 years based on 0.65 million records from 47 LMICs. In the fully adjusted mixed effects model, each 10 µg/m3 increase in life-course averaged exposure to dust PM2.5 was associated with a 9.3% increase in the odds of anemia. The estimated exposure-response association was nonlinear, with a greater effect of dust PM2.5 exposure seen at low concentrations. Applying this association, we found that, in 2017, among all children aged <5 years in the 125 LMICs, dust PM2.5 contributed to 37.98 million cases of anemia. Results indicated that dust PM2.5 contributed a heavier burden than all of the well-identified risk factors did, except for iron deficiency. Our study revealed that long-term exposure to dust PM2.5 can be a novel risk factor, pronouncedly contributed to the burden of child anemia in LMICs, affected by land degradations or arid climate.

Responsive mechanism of Hemerocallis citrina Baroni to complex saline-alkali stress revealed by photosynthetic characteristics and antioxidant regulation.

KEY MESSAGE: Saline-alkali stress induces oxidative damage and photosynthesis inhibition in H. citrina, with a significant downregulation of the expression of photosynthesis- and antioxidant-related genes at high concentration. Soil salinization is a severe abiotic stress that impacts the growth and development of plants. In this study, Hemerocallis citrina Baroni was used to investigate its responsive mechanism to complex saline-alkali stress (NaCl:Na2SO4:NaHCO3:Na2CO3 = 1:9:9:1) for the first time. The growth phenotype, photoprotective mechanism, and antioxidant system of H. citrina were studied combining physiological and transcriptomic techniques. KEGG enrichment and GO analyses revealed significant enrichments of genes related to photosynthesis, chlorophyll degradation and antioxidant enzyme activities, respectively. Moreover, weighted gene co-expression network analysis (WGCNA) found that saline-alkali stress remarkably affected the photosynthetic characteristics and antioxidant system. A total of 29 key genes related to photosynthesis and 29 key genes related to antioxidant enzymes were discovered. High-concentration (250 mmol L-1) stress notably inhibited the expression levels of genes related to light-harvesting complex proteins, photosystem reaction center activity, electron transfer, chlorophyll synthesis, and Calvin cycle in H. citrina leaves. However, most of them were insignificantly changed under low-concentration (100 mmol L-1) stress. In addition, H. citrina leaves under saline-alkali stress exhibited yellow-brown necrotic spots, increased cell membrane permeability and accumulation of reactive oxygen species (ROS) as well as osmolytes. Under 100 mmol L-1 stress, ROS was eliminate by enhancing the activities of antioxidant enzymes. Nevertheless, 250 mmol L-1 stress down-regulated the expression levels of genes encoding antioxidant enzymes, and key enzymes in ascorbate-glutathione (AsA-GSH) cycle as well as thioredoxin-peroxiredoxin (Trx-Prx) pathway, thus inhibiting the activities of these enzymes. In conclusion, 250 mmol L-1 saline-alkali stress caused severe damage to H. citrina mainly by inhibiting photosynthesis and ROS scavenging capacity.

Examining First- and Second-Level Digital Divide at the Intersection of Race/Ethnicity, Gender, and Socioeconomic Status: An Analysis of the National Health and Aging Trends Study.

BACKGROUND AND OBJECTIVES: Significant societal and technological changes in the 2010s called for an up-to-date understanding of the digital divide among older adults in the United States. This trend study aimed to examine the effects of race/ethnicity and the intersecting effects of race/ethnicity with other marginalized identities related to gender, income, education, and occupation on the first- and second-level digital divide. RESEARCH DESIGN AND METHODS: Utilizing a nationally representative sample of older community dwellers from the National Health and Aging Trends Study, we conducted weighted logistic regressions at 3 time points (2011/2013, 2015, and 2019). The first-level digital divide was measured by access to working phones or computers/laptops; the second-level divide was measured by 7 activities in personal task, social, and health-related Internet use. RESULTS: The first-level racial/ethnic digital divide became nonsignificant in 2019, whereas the disparities in all second-level measures persisted. The intersecting effects of race/ethnicity with low education and/or low income became nonsignificant in 2019 for personal-task use. However, the interactions with low education and/or low income became significant for social and health-related use in 2015 and/or 2019. DISCUSSION AND IMPLICATIONS: This study highlights the persistence of the second-level racial/ethnic digital divide among older community dwellers in the United States, especially the exacerbated social and health-related digital divide for people of color with low socioeconomic status. By considering intersections of marginalized social identities, policymakers and stakeholders should develop targeted strategies to bridge the digital divide, promote health outcomes, and reduce health disparities.

Thymoquinone: An Effective Natural Compound for Kidney Protection.

Kidney disease is a common health problem worldwide. Acute or chronic injuries may interfere with kidney functions, eventually resulting in irreversible kidney damage. A number of recent studies have shown that the plant-derived natural products have an extensive potential for renal protection. Thymoquinone (TQ) is an essential compound derived from Nigella Sativa (NS), which is widely applied in the Middle East as a folk medicine. Previous experiments have demonstrated that TQ has a variety of potential pharmacological effects, including anti-oxidant, antibacterial, antitumor, immunomodulatory, and neuroprotective activities. In particular, the prominent renal protective efficacy of TQ has been demonstrated in both in vivo and in vitro experiments. TQ can prevent acute kidney injuries from various xenobiotics through anti-oxidation, anti-inflammatory, and anti-apoptosis effects. In addition, TQ exhibited significant pharmacological effects on renal cell carcinoma, renal fibrosis, and urinary calculi. The essential mechanisms involve scavenging ROS and increasing anti-oxidant activity, decreasing inflammatory mediators, inducing apoptosis, and inhibiting migration and invasion. The purpose of this review is to conclude the pharmacological effects and the potential mechanisms of TQ in renal protection, shedding new light on the exploration of medicinal phyto-protective agents targeting kidneys.

Bridging the Access Gap: A Decade of Narrowing the Digital Divide for Hispanic Older Adults in the United States.

Objectives: This study examines the digital divide between Hispanic and non-Hispanic White older adults in the United States from 2011 to 2021, using an intersectionality perspective. Methods: Eleven waves of data from the National Health and Aging Trend were analyzed through multilevel logistic regression, focusing on the intersection between race/ethnicity and time (measured by survey waves) within gender, education, and income subgroups. The digital divide was measured by Internet access. Results: Despite the enduring digital access gap, the longitudinal analysis revealed a narrowing digital divide between Hispanic and non-Hispanic White older adults, especially those with low education and income. Discussion: The observed trend signifies progress in digital inclusivity initiatives yet highlights ongoing challenges in fully bridging the divide for the Hispanic older adult community. Future efforts should not only focus on access but also on enhancing the effective usage of digital technologies to promote health equity and well-being.

MST1/2 regulates fibro/adipogenic progenitor fate decisions in skeletal muscle regeneration.

Defective skeletal muscle regeneration is often accompanied by fibrosis. Fibroblast/adipose progenitors (FAPs) are important in these processes, however, the regulation of FAP fate decisions is unclear. Here, using inducible conditional knockout mice, we show that blocking mammalian Ste20-like kinases 1/2 (MST1/2) of FAPs prevented apoptosis and reduced interleukin-6 secretion in vivo and in vitro, which impaired myoblast proliferation and differentiation, as well as impaired muscle regeneration. Deletion of Mst1/2 increased co-localization of Yes-associated protein (YAP) with Smad2/3 in nuclei and promoted differentiation of FAPs toward myofibroblasts, resulting in excessive collagen deposition and skeletal muscle fibrosis. Meanwhile, inhibition of MST1/2 increased YAP/Transcriptional co-activator with PDZ-binding motif activation, which promoted activation of the WNT/ß-catenin pathway and impaired the differentiation of FAPs toward adipocytes. These results reveal a new mechanism for MST1/2 action in disrupted skeletal muscle regeneration and fibrosis via regulation of FAP apoptosis and differentiation. MST1/2 is a potential therapeutic target for the treatment of some myopathies.

PEtN-Modified O-Antigen Enhances Shigella Pathogenesis by Promoting Epithelial Cell Invasion and Inhibiting Complement Binding.

Shigellosis poses an ongoing global public health threat. The presence and length of the O-antigen in lipopolysaccharide play critical roles in Shigella pathogenesis. The plasmid-mediated opt gene encodes a phosphoethanolamine (PEtN) transferase that catalyzes the addition of PEtN to the O-antigen of Shigella flexneri serotype X and Y strains, converting them into serotype Xv and Yv strains, respectively. Since 2002, these modified strains have become prevalent in China. Here we demonstrate that PEtN-mediated O-antigen modification in S. flexneri increase the severity of corneal infection in guinea pigs without any adaptive cost. This heightened virulence is associated with epithelial cell adhesion and invasion, as well as an enhanced inflammatory response of macrophage. Notably, PEtN addition allow S. flexneri to attenuate the binding of complement C3 and better resist phagocytosis, potentially contributing to the retention of S. flexneri in the host environment.

Inactivation of MST1/2 Controls Macrophage Polarization to Affect Macrophage-Related Disease via YAP and Non-YAP Mechanisms.

Macrophage polarization is a critical process that regulates in inflammation, pathogen defense, and tissue repair. Here we demonstrate that MST1/2, a core kinase of Hippo pathway and a recently identified regulator of inflammation, plays a significant role in promoting M2 polarization. We provide evidence that inhibition of MST1/2, achieved through either gene-knockout or pharmacological treatment, leads to increased M1 polarization in a YAP-dependent manner, resulting in the development of M1-associated inflammatory disorders. Moreover, MST1/2 inhibition also leads to a substantial reduction in M2 polarization, but this occurs through the STAT6 and MEK/ERK signaling. The STAT6 is independent of YAP, but MEK/ERK is dependent of YAP. Consistent with these observations, both MST1/2-conditional knockout mice and wild-type mice treated with XMU-MP-1, a chemical inhibitor of MST1/2, exhibited reduced M2-related renal fibrosis, while simultaneously displaying enhanced LPS-mediated inflammation and improved clearance of MCR3-modified gram-negative bacteria. These findings uncover a novel role of MST1/2 in regulating macrophage polarization and establish it as a potential therapeutic target for the treatment of macrophage-related fibrotic diseases.

Melatonin Alleviates Lipopolysaccharide-Induced Abnormal Pregnancy through MTNR1B Regulation of m6A.

Pregnancy is a highly intricate and delicate process, where inflammation during early stages may lead to pregnancy loss or defective implantation. Melatonin, primarily produced by the pineal gland, exerts several pharmacological effects. N6-methyladenosine (m6A) is the most prevalent mRNA modification in eukaryotes. This study aimed to investigate the association between melatonin and m6A during pregnancy and elucidate the underlying protective mechanism of melatonin. Melatonin was found to alleviate lipopolysaccharide (LPS)-induced reductions in the number of implantation sites. Additionally, it mitigated the activation of inflammation, autophagy, and apoptosis pathways, thereby protecting the pregnancy process in mice. The study also revealed that melatonin regulates uterine m6A methylation levels and counteracts abnormal changes in m6A modification of various genes following LPS stimulation. Furthermore, melatonin was shown to regulate m6A methylation through melatonin receptor 1B (MTNR1B) and subsequently modulate inflammation, autophagy, and apoptosis through m6A. In conclusion, our study demonstrates that melatonin protects pregnancy by influencing inflammation, autophagy, and apoptosis pathways in an m6A-dependent manner via MTNR1B. These findings provide valuable insights into the mechanisms underlying melatonin's protective effects during pregnancy and may have implications for potential therapeutic strategies in managing pregnancy-related complications.

A Universal Approach for Controllable Synthesis of Homogeneously Alloyed PtM Nanoflowers toward Enhanced Methanol Oxidation.

Platinum (Pt)-based alloys have received considerable attention due to their compositional variability and unique electrochemical properties. However, homogeneous element distribution at the nanoscale, which is beneficial to various electrocatalytic reactions, is still a great challenge. Herein, a universal approach is proposed to synthesize homogeneously alloyed and size-tunable Pt-based nanoflowers utilizing high gravity technology. Owing to the significant intensification of micro-mixing and mass transfer in unique high gravity shearing surroundings, five typical binary/ternary Pt-based nanoflowers are instantaneously achieved at room temperature. As a proof-of-concept, as-synthesized Platinum-Silver nanoflowers (PtAg NFs) demonstrate excellent catalytic performance and anti-CO poisoning ability for anodic methanol oxidation reaction with high mass activity of 1830 mA mgPt -1, 3.5 and 3.2 times higher than those of conventional beaker products and commercial Pt/C, respectively. The experiment in combination with theory calculations suggest that the enhanced performance is due to additional electronic transmission and optimized d-band center of Pt caused by high alloying degree.

The potential role of Hippo pathway regulates cellular metabolism via signaling crosstalk in disease-induced macrophage polarization.

Macrophages polarized into distinct phenotypes play vital roles in inflammatory diseases by clearing pathogens, promoting tissue repair, and maintaining homeostasis. Metabolism serves as a fundamental driver in regulating macrophage polarization, and understanding the interplay between macrophage metabolism and polarization is crucial for unraveling the mechanisms underlying inflammatory diseases. The intricate network of cellular signaling pathway plays a pivotal role in modulating macrophage metabolism, and growing evidence indicates that the Hippo pathway emerges as a central player in network of cellular metabolism signaling. This review aims to explore the impact of macrophage metabolism on polarization and summarize the cell signaling pathways that regulate macrophage metabolism in diseases. Specifically, we highlight the pivotal role of the Hippo pathway as a key regulator of cellular metabolism and reveal its potential relationship with metabolism in macrophage polarization.