Microbacterium azadirachtae CNUC13 Enhances Salt Tolerance in Maize by Modulating Osmotic and Oxidative Stress.

Soil salinization is one of the leading threats to global ecosystems, food security, and crop production. Plant growth-promoting rhizobacteria (PGPRs) are potential bioinoculants that offer an alternative eco-friendly agricultural approach to enhance crop productivity from salt-deteriorating lands. The current work presents bacterial strain CNUC13 from maize rhizosphere soil that exerted several PGPR traits and abiotic stress tolerance. The strain tolerated up to 1000 mM NaCl and 30% polyethylene glycol (PEG) 6000 and showed plant growth-promoting (PGP) traits, including the production of indole-3-acetic acid (IAA) and siderophore as well as phosphate solubilization. Phylogenetic analysis revealed that strain CNUC13 was Microbacterium azadirachtae. Maize plants exposed to high salinity exhibited osmotic and oxidative stresses, inhibition of seed germination, plant growth, and reduction in photosynthetic pigments. However, maize seedlings inoculated with strain CNUC13 resulted in significantly improved germination rates and seedling growth under the salt-stressed condition. Specifically, compared with the untreated control group, CNUC13-treated seedlings exhibited increased biomass, including fresh weight and root system proliferation. CNUC13 treatment also enhanced photosynthetic pigments (chlorophyll and carotenoids), reduced the accumulation of osmotic (proline) and oxidative (hydrogen peroxide and malondialdehyde) stress indicators, and positively influenced the activities of antioxidant enzymes (catalase, superoxide dismutase, and peroxidase). As a result, CNUC13 treatment alleviated oxidative stress and promoted salt tolerance in maize. Overall, this study demonstrates that M. azadirachtae CNUC13 significantly enhances the growth of salt-stressed maize seedlings by improving photosynthetic efficiency, osmotic regulators, oxidative stress resilience, and antioxidant enzyme activity. These findings emphasize the potential of utilizing M. azadirachtae CNUC13 as a bioinoculant to enhance salt stress tolerance in maize, providing an environmentally friendly approach to mitigate the negative effects of salinity and promote sustainable agriculture.

Giant Photoluminescence Enhancement of Monolayer WSe2 Using a Plasmonic Nanocavity with On-Demand Resonance.

Monolayer transition metal dichalcogenides (TMDs) are considered promising building blocks for next-generation photonic and optoelectronic devices, owing to their fascinating optical properties. However, their inherent weak light absorption and low quantum yield severely hinder their practical applications. Here, we report up to 18000-fold photoluminescence (PL) enhancement in a monolayer WSe2-coupled plasmonic nanocavity. A spectroscopy-assisted nanomanipulation technique enables the assembly of a nanocavity with customizable resonances to simultaneously enhance the excitation and emission processes. In particular, precise control over the magnetic cavity mode facilitates spectral and spatial overlap with the exciton, resulting in plasmon-exciton intermediate coupling that approaches the maximum emission rate in the hybrid system. Meanwhile, the cavity mode exhibits high radiation directivity, which overwhelmingly directs surface-normal PL emission and leads to a 17-fold increase in the collection efficiency. Our approach opens up a new avenue to enhance the PL intensity of monolayer TMDs, facilitating their implementation in highly efficient optoelectronic devices.

HWJMSC-EVs promote cartilage regeneration and repair via the ITGB1/TGF-ß/Smad2/3 axis mediated by microfractures.

The current first-line treatment for repairing cartilage defects in clinical practice is the creation of microfractures (MF) to stimulate the release of mesenchymal stem cells (MSCs); however, this method has many limitations. Recent studies have found that MSC-derived extracellular vesicles (MSC-EVs) play an important role in tissue regeneration. This study aimed to verify whether MSC-EVs promote cartilage damage repair mediated by MFs and to explore the repair mechanisms. In vitro experiments showed that human umbilical cord Wharton's jelly MSC-EVs (hWJMSC-EVs) promoted the vitality of chondrocytes and the proliferation and differentiation ability of bone marrow-derived MSCs. This was mainly because hWJMSC-EVs carry integrin beta-1 (ITGB1), and cartilage and bone marrow-derived MSCs overexpress ITGB1 after absorbing EVs, thereby activating the transforming growth factor-ß/Smad2/3 axis. In a rabbit knee joint model of osteochondral defect repair, the injection of different concentrations of hWJMSC-EVs into the joint cavity showed that a concentration of 50 µg/ml significantly improved the formation of transparent cartilage after MF surgery. Extraction of regenerated cartilage revealed that the changes in ITGB1, transforming growth factor-ß, and Smad2/3 were directly proportional to the repair of regenerated cartilage. In summary, this study showed that hWJMSC-EVs promoted cartilage repair after MF surgery.

Model and Data Dual-Driven Double-Point Observation Network for Ultra-Short MI EEG Classification.

Although deep networks have succeeded in various signal classification tasks, the time sequence samples used to train the deep models are usually required to reach a certain length. Especially, in brain computer interface (BCI) research, around 3.5s-long motor imagery (MI) Electroencephalography (EEG) samples are needed to obtain satisfactory classification performance. This time-span requirement of the training samples makes real-time MI BCI systems impossible to implement based on deep networks, which restricts the related researches within laboratory and makes practical application hard to accomplish. To address this issue, a double-point observation deep network (DoNet) is developed to classify ultra-short samples buried in noise. First, an analytical solution is developed theoretically to perform ultra-short signal classification based on double-point couples. Then, a signal-noise model is constructed to study the interference of noise on classification based on double-point couples. Based on which, an independent identical distribution condition is utilized to improve the classification accuracy in a data-driven manner. Combining the theoretical model and data-driven mechanism, DoNet can construct a steady data-distribution for the double-point couples of the samples with the same label. Therefore, the conditional probability of each double-point couple of a test sample can be obtained. With a voting strategy, the samples can be accurately classified by fusing these conditional probabilities. Meanwhile, the noise interference can be suppressed. DoNet has been evaluated on two public EEG datasets. Compared to most state-of-the-art methods, the 1s-long EEG signal classification accuracy has been improved by more than 3%.

[Analysis of a child featuring global developmental delay and autism due to variant of TBR1 gene and a literature review].

OBJECTIVE: To explore the clinical characteristics and genetic basis for a child with global developmental delay and autism. METHODS: A child who had presented at West China Second University Hospital of Sichuan University on April 13, 2021 was selected as the study subject. Clinical manifestations, laboratory examination and result of genetic testing were analyzed. RESULTS: The main symptoms of the child had included cognitive, language and motor delay, autism and epilepsy. Electroencephalogram revealed multiple focal discharges in both waking and sleeping stages, with the remarkable one seen at the sleeping stage. Cranial MRI showed pachygyria and local cortical thickening, Whole exome sequencing (WES) revealed that the child has harbored a heterozygous c.1589_1595dup (p.Gly533Leufs*143) frameshifting variant in the TBR1 gene (OMIM 604616). Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be likely pathogenic (PS2+PVS1_Supporting+PM2_Supporting). After treated with levetiracetam and rehabilitation training, the child did not have seizure in the past 5 months, and his motor development has also significantly improved. CONCLUSION: The c.1589_1595dup variant of the TBR1 gene probably underlay the disease in this patient.

Safety and efficacy of phage application in bacterial decolonisation: a systematic review.

Colonisation by bacterial pathogens typically precedes invasive infection and seeds transmission. Thus, effective decolonisation strategies are urgently needed. The literature reports attempts to use phages for decolonisation. To assess the in-vivo efficacy and safety of phages for bacterial decolonisation, we performed a systematic review by identifying relevant studies to assess the in-vivo efficacy and safety of phages for bacterial decolonisation. We searched PubMed, Embase (Ovid), MEDLINE (Ovid), Web of Science, and the Cochrane Library to identify relevant articles published between Jan 1, 1990, and May 12, 2023, without language restrictions. We included studies that assessed the efficacy of phage for bacterial decolonisation in humans or vertebrate animal models. This systematic review is registered with PROSPERO, CRD42023457637. We identified 6694 articles, of which 56 (51 animal studies and five clinical reports) met the predetermined selection criteria and were included in the final analysis. The gastrointestinal tract (n=49, 88%) was the most studied bacterial colonisation site, and other sites were central venous catheters, lung, nose, skin, and urinary tract. Of the 56 included studies, the bacterial load at the colonisation site was reported to decrease significantly in 45 (80%) studies, but only five described eradication of the target bacteria. 15 studies reported the safety of phages for decolonisation. No obvious adverse events were reported in both the short-term and long-term observation period. Given the increasing life-threatening risks posed by bacteria that are difficult to treat, phages could be an alternative option for bacterial decolonisation, although further optimisation is required before their application to meet clinical needs.

Safety, tolerability, pharmacokinetics and pharmacokinetic-pharmacodynamic modeling of cetagliptin in patients with type 2 diabetes mellitus.

Aims: To evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of cetagliptin (CAS number:2243737-33-7) in Chinese patients with type 2 diabetes mellitus (T2DM). A population PK/PD model was developed to quantify the PK and PD characteristics of cetagliptin in patients. Materials and methods: 32 Chinese adults with T2DM were enrolled in this study. The subjects were randomly assigned to receive either cetagliptin (50 mg or 100 mg), placebo, or sitagliptin (100 mg) once daily for 14 days. Blood samples were collected for PK and PD analysis. Effects on glucose, insulin, C-peptide, and glucagon were evaluated following an oral glucose tolerance test (OGTT) (day15). Effects on HbA1c and glycated albumin (GA), and safety assessments were also conducted. Meanwhile, a population PK/PD model was developed by a sequential two-step analysis approach using Phoenix. Results: Following multiple oral doses, cetagliptin was rapidly absorbed and the mean half-life were 34.9-41.9 h. Steady-state conditions were achieved after 1 week of daily dosing and the accumulation was modest. The intensity and duration of DPP-4 inhibition induced by 50 mg cetagliptin were comparable with those induced by sitagliptin, and 100 mg cetagliptin showed a much longer sustained DPP-4 inhibition (≥80%) than sitagliptin. Compared with placebo group, plasma active GLP-1 AUEC0-24h increased by 2.20- and 3.36-fold in the 50 mg and 100 mg cetagliptin groups. A decrease of plasma glucose and increase of insulin and C-peptide were observed following OGTT in cetagliptin groups. Meanwhile, a tendency of reduced GA was observed, whereas no decreasing trend was observed in HbA1c. All adverse events related to cetagliptin and sitagliptin were assessed as mild. A population PK/PD model was successfully established. The two-compartment model and Sigmoid-Emax model could fit the observed data well. Total bilirubin (TBIL) was a covariate of volume of peripheral compartment distribution (V2), and V2 increased with the increase of TBIL. Conclusions: Cetagliptin was well tolerated, inhibited plasma DPP-4 activity, increased plasma active GLP-1 levels, and exhibited a certain trend of glucose-lowering effect in patients with T2DM. The established population PK/PD model adequately described the PK and PD characteristics of cetagliptin.

Helical Nanographenes Bearing Pentagon-Heptagon Pairs by Stepwise Dehydrocyclization.

The incorporation of pentagon-heptagon pairs into helical nanographenes lacks a facile synthetic route, and the impact of these pairs on chiroptical properties remains unclear. In this study, a method for the stepwise construction of pentagon-heptagon pairs in helical nanographenes by the dehydrogenation of [6]helicene units was developed. Three helical nanographenes containing pentagon-heptagon pairs were synthesized and characterized using this approach. A wide variation in the molecular geometries and photophysical properties of these helical nanographenes was observed, with changes in the helical length of these structures and the introduction of the pentagon-heptagon pairs. The embedded pentagon-heptagon pairs reduced the oxidation potential of the synthesized helical nanographenes. The high isomerization energy barriers enabled the chiral resolution of the helicene enantiomers. Chiroptical investigations revealed remarkably enhanced circularly polarized luminescence and luminescence dissymmetry factors with an increasing number of the pentagon-heptagon pairs.

α-Solanine attenuates chondrocyte pyroptosis to improve osteoarthritis via suppressing NF-κB pathway.

α-Solanine has been shown to exhibit anti-inflammatory and anti-tumour properties; however, its efficacy in treating osteoarthritis (OA) remains ambiguous. The study aimed to evaluate the therapeutic effects of α-solanine on OA development in a mouse OA model. The OA mice were subjected to varying concentrations of α-solanine, and various assessments were implemented to assess OA progression. We found that α-solanine significantly reduced osteophyte formation, subchondral sclerosis and OARSI score. And it decreased proteoglycan loss and calcification in articular cartilage. Specifically, α-solanine inhibited extracellular matrix degradation by downregulating collagen 10, matrix metalloproteinase 3 and 13, and upregulating collagen 2. Importantly, α-solanine reversed chondrocyte pyroptosis phenotype in articular cartilage of OA mice by inhibiting the elevated expressions of Caspase-1, Gsdmd and IL-1ß, while also mitigating aberrant angiogenesis and sensory innervation in subchondral bone. Mechanistically, α-solanine notably hindered the early stages of OA progression by reducing I-κB phosphorylation and nuclear translocation of p65, thereby inactivating NF-κB signalling. Our findings demonstrate the capability of α-solanine to disrupt chondrocyte pyroptosis and sensory innervation, thereby improving osteoarthritic pathological progress by inhibiting NF-κB signalling. These results suggest that α-solanine could serve as a promising therapeutic agent for OA treatment.

Reporting of tumor lysis syndrome with targeted therapy for hepatic cancer in the FDA adverse events reporting system.

BACKGROUND: Hepatic cancer is a common cancer in clinical practice. Current drug therapies for this condition include targeted therapy, chemotherapy, and immunotherapy. Tumor lysis syndrome (TLS) is the most serious complication of oncology treatment. According to the literature, several cases reported TLS occurred with targeted therapies for hepatic cancer. METHODS: Reporting odds ratio and information component were used to measure the disproportionate signals for TLS associated with targeted therapies, using data from the FDA's Adverse Event Reporting System (FAERS). A stepwise sensitivity analysis was conducted to test the robustness of signals. Time-to-onset analysis was used to describe the latency of TLS events associated with targeted therapies. The Bradford Hill criteria were used to perform a global assessment of the evidence. RESULTS: Sorafenib, lenvatinib, cabozantinib, and bevacizumab showed higher disproportionate signals for TLS than chemotherapy. The median number of days to TLS occurrence after drug therapy was 5.5, 6.5, and 6.5 days for sorafenib, lenvatinib, and bevacizumab, respectively. CONCLUSIONS: There is a significant association between tumor lysis syndrome and targeted therapies for hepatic carcinoma, with particularly strong signals for sorafenib and lenvatinib. Clinicians should be aware of the potential for tumor lysis syndrome in targeted therapies for hepatic carcinoma.

Atrazine exposure promotes cardiomyocyte pyroptosis to exacerbate cardiotoxicity by activating NF-κB pathway.

Atrazine is a ubiquitous herbicide with persistent environmental presence and accumulation in the food chain, posing potential health hazards to organisms. Increasing evidence suggests that atrazine may have detrimental effects on various organ systems, including the nervous, digestive, and immune systems. However, the specific toxicity and underlying mechanism of atrazine-induced cardiac injury remain obscure. In this study, 4-week-old male C57BL/6 mice were administered atrazine via intragastric administration at doses of 50 and 200 mg/kg for 4 and 8 weeks, respectively. Our findings showed that atrazine exposure led to cardiac fibrosis, as evidenced by elevated heart index and histopathological scores, extensive myofiber damage, and interstitial collagen deposition. Moreover, atrazine induced cardiomyocyte apoptosis, macrophage infiltration, and excessive production of inflammatory factors. Importantly, atrazine upregulated the expressions of crucial pyroptosis proteins, including NLRP3, ASC, CASPASE1, and GSDMD, via the activation of NF-κB pathway, thus promoting cardiomyocyte pyroptosis. Collectively, our findings provide novel evidence demonstrating that atrazine may exacerbate myocardial fibrosis by inducing cardiomyocyte pyroptosis, highlighting its potential role in the development of cardiac fibrosis.

Safety and efficacy of a phage cocktail on murine wound infections caused by carbapenem-resistant Klebsiella pneumoniae.

OBJECTIVES: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a leading pathogen causing difficult-to-treat, healthcare-associated wound infections. Phages are an alternative approach against CRKP. This study established murine wound infection models with a CRKP clinical strain of sequence type 11 and capsular type KL64, which is the dominant type in China, carrying genes encoding KPC-2 and NDM-1 carbapenemases. METHODS: A cocktail was made comprising three lytic phages of different viral families against the strain. The phage cocktail restricted bacterial growth for 10 hours in vitro. The efficacy and safety of the phage cocktail in treating a murine wound CRKP infection were then evaluated. Mice were randomly assigned into four groups (16 for each) comprising a phage treatment group, infected with bacteria and 30 minutes later with phages, and three control groups administered with PBS (negative control), bacteria (infection control), or phages (phage control) on the wound. Wound tissues were processed for counting bacterial loads on days 1, 3, and 7 post-infection and examined for histopathological change on days 3 and 7. Two remaining mice in each group were monitored for wound healing until day 14. RESULTS: Compared with the infection control group, the wound bacterial load in the phage treatment group decreased by 4.95 × 102 CFU/g (> 100-fold; P < 0.05) at day 7 post-treatment, and wounds healed on day 10, as opposed to day 14 in the infection control group. No adverse events associated with phages were observed. CONCLUSION: The phage cocktail significantly reduced the wound bacterial load and promoted wound healing with good safety.

Copper-doped bismuth oxychloride nanosheets assembled into sphere-like morphology for improved photocatalytic inactivation of drug-resistant bacteria.

The devastating microbiological contamination as well as emerging drug-resistant bacteria has posed severe threats to the ecosystem and public health, which propels the continuous exploitation of safe yet efficient disinfection products and technology. Here, copper doping engineered bismuth oxychloride (Cu-BiOCl) nanocomposite with a hierarchical spherical structure was successfully prepared. It was found that due to the exposure of abundant active sites for the adsorption of both bacteria cells and molecular oxygen in the structure, the obtained Cu-BiOCl with nanosheets assembled into sphere-like morphology exhibited remarkable photocatalytic antibacterial effects. In particular, compared to the pure BiOCl, composite Cu-BiOCl possessed improved antibacterial effects against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Methicillin-resistant Staphylococcus aureus (MRSA). The combination of physicochemical characterizations and theoretical calculations has revealed that copper doping significantly promoted the light absorbance, inhibited the recombination of electron-hole pairs, and enhanced molecular oxygen adsorption, which resulted in more generation of active species including reactive oxygen species (ROS) and h+ to achieve superior photocatalytic bacterial inactivation. Finally, transcriptome analysis on MRSA pinpointed photocatalytic inactivation induced by Cu-BiOCl may retard largely the development of drug-resistance. Therefore, the built spherical Cu-BiOCl nanocomposite has provided an ecofriendly, economical and robust strategy for the efficient removal of drug-resistant bacteria with promising potentials for environmental and healthcare utilizations.

Targeting cellular senescence in senile osteoporosis: therapeutic potential of traditional Chinese medicine.

Senile osteoporosis (SOP) is a prevalent manifestation of age-related bone disorders, resulting from the dysregulation between osteoblast (OB)-mediated bone formation and osteoclast (OC)-mediated bone resorption, coupled with the escalating burden of cellular senescence. Traditional Chinese medicine (TCM) herbs, renowned for their remarkable attributes encompassing excellent tolerability, low toxicity, heightened efficacy, and minimal adverse reactions, have gained considerable traction in OP treatment. Emerging evidence substantiates the therapeutic benefits of various TCM formulations and their active constituents, including Zuogui wan, Fructus Ligustri Lucidi, and Resveratrol, in targeting cellular senescence to address SOP. However, a comprehensive review focusing on the therapeutic efficacy of TCM against SOP, with a particular emphasis on senescence, is currently lacking. In this review, we illuminate the pivotal involvement of cellular senescence in SOP and present a comprehensive exploration of TCM formulations and their active ingredients derived from TCM, delineating their potential in SOP treatment through their anti-senescence properties. Notably, we highlight their profound effects on distinct aging models that simulate SOP and various senescence characteristics. Finally, we provide a forward-looking discussion on utilizing TCM as a strategy for targeting cellular senescence and advancing SOP treatment. Our objective is to contribute to the unveiling of safer and more efficacious therapeutic agents for managing SOP.

Detecting anomalous electricity consumption with transformer and synthesized anomalies.

Non-technical losses are consistently a troubling issue for power suppliers. With the application and popularization of smart grid and advanced measurement systems, it has become possible to use data-driven methods to detect anomalous electricity consumption to reduce non-technical losses. A range of machine learning models have been utilized for detecting anomalous electricity consumption and have achieved promising results. However, with the evolution of techniques like electricity theft, coupled with the exponential increase in electricity consumption data, new challenges are constantly being posed for anomalous electricity consumption detection. We propose a Transformer-based method for detecting anomalous electricity consumption. The Transformer is composed of multi-head attention, layer normalization, point-wise feed-forward network, etc., which can effectively handle electricity consumption time-series data. Meanwhile, to alleviate the problem of imbalanced training data between anomalous and normal electricity consumption, we propose a method for synthesizing anomalies. The experimental results demonstrate that our proposed Transformer-based method outperforms the state-of-the-art methods in detecting anomalous electricity consumption, achieving a precision of 93.9%, a recall of 96.3%, an F1-score of 0.951, and an accuracy of 95.6% on a dataset released by the State Grid Corporation of China.

Insights into myopic choroidal neovascularization based on quantitative proteomics analysis of the aqueous humor.

BACKGROUND: Previous studies on the biomarkers of pathologic myopia choroidal neovascularization (pmCNV) development merely detected limited types of proteins and provide a meagre illustration of the underlying pathways. Hence, a landscape of protein changes in the aqueous humor (AH) of pmCNV patients is lacking. Here, to explore the potential mechanisms and biomarkers of pmCNV, we analyzed the clinical data and protein profile among atrophic (A) lesions, tractional lesions (T) and neovascular (N) lesions in myopic patients based on the ATN grading system for myopic maculopathy (MM). RESULTS: After investigating demographic data of our patients, a correlation was found between A and N lesions (R = 0.5753, P < 0.0001). Accordingly, groups were divided into patients without MM, patients with myopic atrophic maculopathy (MAM), and patients with pmCNV (N2a lesion). In proteomics analysis, the increased protein level of GFAP and complement-associated molecules in AH samples of the 3 groups also indicated that MAM and pmCNV shared similar characteristics. The GO enrichment and KEGG pathway analysis were performed, which mapped that differential expressed proteins mainly engaged in JAK-STAT pathway between the pmCNV group and two controls. Furthermore, we identified several potential biomarkers for pmCNV, including FCN3, GFAP, EGFR, SFRP3, PPP2R1A, SLIT2, and CD248. CONCLUSIONS: Atrophic lesions under pathologic myopic conditions demonstrated similarities to neovascularization development. Potential biomarkers including GFAP were associated with the pathogenesis of pmCNV. In summary, our study provides new insights for further research on pmCNV development.

Erbin accelerates TFEB-mediated lysosome biogenesis and autophagy and alleviates sepsis-induced inflammatory responses and organ injuries.

Mounting attention has been focused on defects of the autophagy-lysosomal pathway in sepsis, however, the precise mechanisms governing the autophagy-lysosomal process in sepsis are poorly known. We have previously reported that Erbin deficiency aggravated the inflammatory response and organ injuries caused by sepsis. In the present study, we found that Erbin knockout impaired the autophagy process in both muramyl dipeptide (MDP)-induced bone marrow-derived macrophages (BMDMs) and sepsis mouse liver and lung, as detected by the accumulation of LC3-II and SQSTM1/p62, and autophagosomes. Pretreatment with autophagy inhibitor chloroquine (CQ) further aggravated inflammatory response and organ injuries in vivo and in vitro sepsis model. We also observed that the impaired lysosomal function mediated autophagic blockade, as detected by the decreased expression of ATP6V, cathepsin B (CTSB) and LAMP2 protein. Immunoprecipitation revealed that the C-terminal of Erbin (aa 391-964) interacts with the N-terminal of transcription factor EB (TFEB) (aa 1-247), and affects the stability of TFEB-14-3-3 and TFEB-PPP3CB complexes and the phosphorylation status of TFEB, thereby promote the nucleus translocation of TFEB and the TFEB target genes transcription. Thus, our study suggested that Erbin alleviated sepsis-induced inflammatory responses and organ injuries by rescuing dysfunction of the autophagy-lysosomal pathway through TFEB-14-3-3 and TFEB-PPP3CB pathway.

"Leader-Follower" Dynamic Perturbation Manipulates Multi-Item Working Memory in Humans.

Manipulating working memory (WM) is a central yet challenging notion. Previous studies suggest that WM items with varied memory strengths reactivate at different latencies, supporting a time-based mechanism. Motivated by this view, here we developed a purely bottom-up "Leader-Follower" behavioral approach to manipulate WM in humans. Specifically, task-irrelevant flickering color disks that are bound to each of the memorized items are presented during the delay period, and the ongoing luminance sequences of the color disks follow a Leader-Follower relationship, that is, a hundreds of milliseconds temporal lag. We show that this dynamic behavioral approach leads to better memory performance for the item associated with the temporally advanced luminance sequence (Leader) than the item with the temporally lagged luminance sequence (Follower), yet with limited effectiveness. Together, our findings constitute evidence for the essential role of temporal dynamics in WM operation and offer a promising, noninvasive WM manipulation approach.

The impact of three carbapenems at a single-day dose on intestinal colonization resistance against carbapenem-resistant Klebsiella pneumoniae.

IMPORTANCE: The intestinal colonization of carbapenem-resistant Klebsiella pneumoniae (CRKP) is an important source of clinical infection. Our research showed that even single-day dose use of carbapenems caused CRKP colonization and continuous bacterial shedding, which reminds clinical doctors to prescribe carbapenems cautiously. Whenever possible, ertapenem should be the preferred choice over other carbapenems especially when the identified or highly suspected pathogens can be effectively targeted by ertapenem.

Aconine attenuates osteoclast-mediated bone resorption and ferroptosis to improve osteoporosis via inhibiting NF-κB signaling.

Osteoporosis (OP), a prevalent public health concern primarily caused by osteoclast-induced bone resorption, requires potential therapeutic interventions. Natural compounds show potential as therapeutics for postmenopausal OP. Emerging evidence from in vitro osteoclastogenesis assay suggests that aconine (AC) serves as an osteoclast differentiation regulator without causing cytotoxicity. However, the in vivo functions of AC in various OP models need clarification. To address this, we administered intraperitoneal injections of AC to ovariectomy (OVX)-induced OP mice for 8 weeks and found that AC effectively reversed the OP phenotype of OVX mice, leading to a reduction in vertebral bone loss and restoration of high bone turnover markers. Specifically, AC significantly suppressed osteoclastogenesis in vivo and in vitro by decreasing the expression of osteoclast-specific genes such as NFATc1, c-Fos, Cathepsin K, and Mmp9. Importantly, AC can regulate osteoclast ferroptosis by suppressing Gpx4 and upregulating Acsl4, which is achieved through inhibition of the phosphorylation of I-κB and p65 in the NF-κB signaling pathway. These findings suggest that AC is a potential therapeutic option for managing OP by suppressing NF-κB signaling-mediated osteoclast ferroptosis and formation.