UNETR++: Delving into Efficient and Accurate 3D Medical Image Segmentation.

Owing to the success of transformer models, recent works study their applicability in 3D medical segmentation tasks. Within the transformer models, the self-attention mechanism is one of the main building blocks that strives to capture long-range dependencies, compared to the local convolutional-based design. However, the self-attention operation has quadratic complexity which proves to be a computational bottleneck, especially in volumetric medical imaging, where the inputs are 3D with numerous slices. In this paper, we propose a 3D medical image segmentation approach, named UNETR++, that offers both high-quality segmentation masks as well as efficiency in terms of parameters, compute cost, and inference speed. The core of our design is the introduction of a novel efficient paired attention (EPA) block that efficiently learns spatial and channel-wise discriminative features using a pair of inter-dependent branches based on spatial and channel attention. Our spatial attention formulation is efficient and has linear complexity with respect to the input. To enable communication between spatial and channel-focused branches, we share the weights of query and key mapping functions that provide a complimentary benefit (paired attention), while also reducing the complexity. Our extensive evaluations on five benchmarks, Synapse, BTCV, ACDC, BraTS, and Decathlon-Lung, reveal the effectiveness of our contributions in terms of both efficiency and accuracy. On Synapse, our UNETR++ sets a new state-of-the-art with a Dice Score of 87.2%, while significantly reducing parameters and FLOPs by over 71%, compared to the best method in the literature. Our code and models are available at: https://tinyurl.com/2p87x5xn.

Exploring the Localization of Siderophore-Mediated Cargo Delivery in Gram-Negative Bacteria Using 3-Hydroxypyridin-4(1H)-one-Fluorescein Probes.

The design of siderophore-antibiotic conjugates is a promising strategy to overcome drug resistance in negative bacteria. However, accumulating studies have shown that only those antibiotics acting on the cell wall or cell membrane multiply their antibacterial effects when coupled with siderophores, while antibiotics acting on targets in the cytoplasm of bacteria do not show an obvious enhancement of their antibacterial effects when coupled with siderophores. To explore the causes of this phenomenon, we synthesized several conjugate probes using 3-hydroxypyridin-4(1H)-ones as siderophores and replacing the antibiotic cargo with 5-carboxyfluorescein (5-FAM) or malachite green (MG) cargo. By monitoring changes in the fluorescence intensity of FAM conjugate 20 in bacteria, the translocation of the conjugate across the outer membranes of Gram-negative pathogens was confirmed. Further, the use of the fluorogen activating protein(FAP)/MG system revealed that 3-hydroxypyridin-4(1H)-one-MG conjugate 26 was ultimately distributed mainly in the periplasm rather than being translocated into the cytosol of Escherichia coli and Pseudomonas aeruginosa PAO1. Additional mechanistic studies suggested that the uptake of the conjugate involved the siderophore-dependent iron transport pathway and the 3-hydroxypyridin-4(1H)-ones siderophore receptor-dependent mechanism. Meanwhile, we demonstrated that the conjugation of 3-hydroxypyridin-4(1H)-ones to the fluorescein 5-FAM can reduce the possibility of the conjugates crossing the membrane layers of mammalian Vero cells by passive diffusion, and the advantages of the mono-3-hydroxypyridin-4(1H)-ones as a delivery vehicle in the design of conjugates compared to the tri-3-hydroxypyridin-4(1H)-ones. Overall, this work reveals the localization rules of 3-hydroxypyridin-4(1H)-ones as siderophores to deliver the cargo into Gram-negative bacteria. It provides a theoretical basis for the subsequent design of siderophore-antibiotic conjugates, especially based on 3-hydroxypyridin-4(1H)-ones as siderophores.

Establishment of a Simple, Sensitive, and Specific Salmonella Detection Method Based on Recombinase-Aided Amplification Combined with dsDNA-Specific Nucleases.

Salmonella is a common foodborne pathogen that can cause food poisoning, posing a serious threat to human health. Therefore, quickly, sensitively, and accurately detecting Salmonella is crucial to ensuring food safety. For the Salmonella hilA gene, we designed Recombinase-aided amplification (RAA) primers and dsDNA-specific nuclease (DNase) probes. The ideal primer and probe combination was found when conditions were optimized. Under UV light, a visual Salmonella detection technique (RAA-dsDNase) was developed. Additionally, the RAA-dsDNase was modified to further reduce pollution hazards and simplify operations. One-pot RAA-dsDNase-UV or one-pot RAA-dsDNase-LFD was developed as a Salmonella detection method, using UV or a lateral flow dipstick (LFD) for result observation. Among them, one-pot RAA-dsDNase and one-pot RAA-dsDNase-LFD had detection times of 50 min and 60 min, respectively, for detecting Salmonella genomic DNA. One-pot RAA-dsDNase-UV had a detection limit of 101 copies/µL and 101 CFU/mL, while one-pot RAA-dsDNase-LFD had a sensitivity of 102 copies/µL and 102 CFU/mL. One-pot RAA-dsDNase-UV and one-pot RAA-dsDNase-LFD assays may identify 17 specific Salmonella serovars witho ut causing a cross-reaction with the remaining 8 bacteria, which include E. coli. Furthermore, Salmonella in tissue and milk samples has been reliably detected using both approaches. Overall, the detection method developed in this study can quickly, sensitively, and accurately detect Salmonella, and it is expected to become an important detection tool for the prevention and control of Salmonella in the future.

Magnolin inhibits intestinal epithelial cell apoptosis alleviating Crohn's disease-like colitis by suppressing the PI3K/AKT signalling pathway.

BACKGROUND AND AIMS: Previous reports have shown that preventing excessive intestinal epithelial cell (IEC) apoptosis is a crucial approach for protecting the intestinal barrier in patients with Crohn's disease (CD). Magnolin (MGL) has various biological activities, including antiapoptotic activities, but its role in CD has largely not been determined. This study investigated how MGL impacts CD-like colitis and the underlying mechanism involved. METHODS: Mice were treated with TNBS to establish a disease model, and these mice were used to assess the therapeutic effects of MGL on CD-like colitis. TNF-α-treated colon organoids were used to evaluate the impact of MGL on intestinal barrier function and IEC apoptosis. Enrichment analysis was performed to examine the potential pathways through which MGL inhibits IEC apoptosis. Finally, rescue experiments showed the mechanism by which MGL suppresses IEC apoptosis. RESULTS: The animal experiments demonstrated that MGL treatment alleviated the weight loss, colon shortening, elevated disease activity index (DAI) scores, increased colitis histological scores and upregulated inflammatory factor expression that were observed in model mice. MGL ameliorated intestinal barrier dysfunction and the loss of tight junction (TJ) proteins (ZO-1 and Claudin-1) by inhibiting IEC apoptosis in both TNBS-treated mice and TNF-α-treated colon organoids. MGL inhibited the PI3K/AKT signalling pathway, thus safeguarding the intestinal barrier and alleviating CD-like colitis in vivo and in vitro. CONCLUSIONS: MGL improves the intestinal barrier integrity and prevents CD-like colitis by inhibiting IEC apoptosis. The potential mechanism of its anti-apoptotic impact on IECs could be associated with the PI3K/AKT pathway, presenting novel approaches and avenues for the clinical management of CD.

Neuro-stimulating effect of Citri Reticulata Pericarpium Viride essential oil through regulating Glu/NMDAR on olfactory bulb to improve anxiety-like behavior.

ETHNOPHARMACOLOGICAL RELEVANCE: Citri Reticulata Pericarpium Viride (also known Qing-Pi or QP) is a plant in the Rutaceae family, QP is a traditional Qi-regulating medicine in Chinese medicine that is compatible with other Chinese medicine components and has extensive clinical practice in treating anxiety and depression. Reports on the pharmacological effects of QP have demonstrated its neuroprotective effects and antioxidant capacities. Numerous pharmacological benefits of QP are attributed to its antioxidant abilities. Anxiety disorders are a broadly defined category of mental illnesses. Oxidative stress and an imbalance in the antioxidant defense system are typical pathological features of these disorders. AIM OF THE STUDY: The aim of this study was to evaluate the effects of QP essential oil on anxiety using animal models and investigate the underlying neurobiological mechanisms. MATERIALS AND METHODS: This study aimed to develop an animal model of anxiety using chronic restraint stress and investigate the effects of inhalation of Citri Reticulata Pericarpium Viride essential oil on anxiety-like behavior, olfactory function, and olfactory bulb neurogenesis in mice with anxiety. RESULTS: The results showed that long-term chronic restraint stimulation caused a decrease in olfactory function, significant anxiety-like behavior, and a notable reduction in the number of neurons in the olfactory bulb. However, inhalation of Citri Reticulata Pericarpium Viride essential oil reversed these effects, improving the olfactory function, neuro-stimulating effect, alleviating anxiety-like behavior, and regulating theta (4-12Hz) oscillation in the hippocampus DG area. These effects were associated with changes in the expression levels of glutamate receptor NMDAR and NeuN in olfactory bulb. CONCLUSIONS: The study revealed that mice with anxiety induced by chronic restraint stress exhibited significant olfactory dysfunction, providing strong evidence for the causal relationship between anxiety disorders and olfactory dysfunction. Moreover, QP essential oil has the potential to be developed as a therapeutic drug for anxiety disorders, in addition to its role as a complementary anxiolytic.

Br-Vacancies Induced Variable Ranging Hopping Conduction in High-Order Topological Insulator Bi4Br4.

The defects have a remarkable influence on the electronic structures and the electric transport behaviors of the matter, providing the additional means to engineering their physical properties. In this work, a comprehensive study on the effect of Br-vacancies on the electronic structures and transport behaviors in the high-order topological insulator Bi4Br4 is performed by the combined techniques of the scanning tunneling microscopy (STM), angle-resolved photoemission spectroscopy (ARPES), and physical properties measurement system along with the first-principle calculations. The STM results show the defects on the cleaved surface of a single crystal and reveal that the defects are correlated to the Br-vacancies with the support of the simulated STM images. The role of the Br-vacancies in the modulation of the band structures has been identified by ARPES spectra and the calculated energy-momentum dispersion. The relationship between the Br-vacancies and the semiconducting-like transport behaviors at low temperature has been established, implying a Mott variable ranging hopping conduction in Bi4Br4. The work not only resolves the unclear transport behaviors in this matter, but also paves a way to modulate the electric conduction path by the defects engineering.

Strain-induced ferroelectric polarization reversal without undergoing geometric inversion in blue SiSe monolayer.

Ferroelectricity in two-dimensional (2D) systems generally arises from phonons and has been widely investigated. On the contrary, electronic ferroelectricity in 2D systems has been rarely studied. Using first-principles calculations, the ferroelectric behavior of the buckled blue SiSe monolayer under strain are explored. It is found that the direction of the out-of-plane ferroelectric polarization can be reversed by applying an in-plane strain. And such polarization switching is realized without undergoing geometric inversion. Besides, the strain-triggered polarization reversal emerges in both biaxial and uniaxial strain cases, indicating it is an intrinsic feature of such a system. Further analysis shows that the polarization switching is the result of the reversal of the magnitudes of the positive and negative charge center vectors. And the variation of buckling is found to play an important role, which results in the switch. Moreover, a non-monotonic variation of band gap with strain is revealed. Our findings throws light on the investigation of novel electronic ferroelectric systems.

Association between life's essential 8 and frailty status among cancer survivors in the United States: a cross-sectional analysis.

BACKGROUND: Frailty not only affects disease survival but also impacts the long-term function and quality life of all adults diagnosed with and/or treated for cancer.The American Heart Association has introduced Life's Essential 8 (LE8) as a novel metric for assessing cardiovascular health. Currently, LE8's application in evaluating the frailty of cancer survivors remains unreported. This research seeks to explore the connection between LE8 scores and frailty levels in cancer survivors across the United States, thereby addressing a significant void in existing studies. METHODS: This study analyzed data from cancer survivors enrolled in the National Health and Nutrition Examination Surveys (NHANES) spanning the years 2005 to 2018, providing a comprehensive dataset. Multivariable logistic regression models were used to examine the linkage between LE8 rankings and frailty condition in cancer survivors. Furthermore, the study delved deeper into this correlation using restricted cubic spline (RCS) curves and subgroup analyses. RESULTS: In the fully adjusted model, an increased LE8 level was closely associated with a reduced odds ratio of frailty among cancer survivors, with an OR of 0.95 (95% CI: 0.94-0.96, p < 0.0001).This pattern persisted across different categorizations of LE8 into low, moderate, and high groups, demonstrating a consistent trend. The analysis revealed a non-linear relationship between LE8 scores and frailty status, further supporting a straightforward association (p-value for non-linearity = 0.0729). CONCLUSION: Studies have found that the higher the LE8 score, the less likely a cancer patient is to develop debilitating symptoms.This indicates that the LE8 scores may provide an opportunity for interventions aimed at improving the prognosis of cancer patients.

A clinical-radiomics nomogram based on dual-layer spectral detector CT to predict cancer stage in pancreatic ductal adenocarcinoma.

BACKGROUND: This study aimed to evaluate the efficacy of radiomics signatures derived from polyenergetic images (PEIs) and virtual monoenergetic images (VMIs) obtained through dual-layer spectral detector CT (DLCT). Moreover, it sought to develop a clinical-radiomics nomogram based on DLCT for predicting cancer stage (early stage: stage I-II, advanced stage: stage III-IV) in pancreatic ductal adenocarcinoma (PDAC). METHODS: A total of 173 patients histopathologically diagnosed with PDAC and who underwent contrast-enhanced DLCT were enrolled in this study. Among them, 49 were in the early stage, and 124 were in the advanced stage. Patients were randomly categorized into training (n = 122) and test (n = 51) cohorts at a 7:3 ratio. Radiomics features were extracted from PEIs and 40-keV VMIs were reconstructed at both arterial and portal venous phases. Radiomics signatures were constructed based on both PEIs and 40-keV VMIs. A radiomics nomogram was developed by integrating the 40-keV VMI-based radiomics signature with selected clinical predictors. The performance of the nomogram was assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curves analysis (DCA). RESULTS: The PEI-based radiomics signature demonstrated satisfactory diagnostic efficacy, with the areas under the ROC curves (AUCs) of 0.92 in both the training and test cohorts. The optimal radiomics signature was based on 40-keV VMIs, with AUCs of 0.96 and 0.94 in the training and test cohorts. The nomogram, which integrated a 40-keV VMI-based radiomics signature with two clinical parameters (tumour diameter and normalized iodine density at the portal venous phase), demonstrated promising calibration and discrimination in both the training and test cohorts (0.97 and 0.91, respectively). DCA indicated that the clinical-radiomics nomogram provided the most significant clinical benefit. CONCLUSIONS: The radiomics signature derived from 40-keV VMI and the clinical-radiomics nomogram based on DLCT both exhibited exceptional performance in distinguishing early from advanced stages in PDAC, aiding clinical decision-making for patients with this condition.

Body mass weighted PSA levels, new markers to predict locally advanced prostate cancer after prostatectomy.

BACKGROUND: PSA remains the most useful marker for screening, risk categorization, and follow-up in patients with prostate cancer. In the obese population, several studies have revealed that obesity may not only inversely interfere with the concentration of PSA, but also increase the risk of prostate cancer. Thus, we considered using the Body mass weighted PSA levels, presented as serum PSA concentration multiplied by body weight or BMI, instead of traditional PSA concentration, as potential markers to predict locally advanced prostate cancer after prostatectomy. METHODS: We retrospectively collected and analyzed data acquired from a single institute at which robot-assisted laparoscopic radical prostatectomy was performed. A total of 174 patients underwent radical prostatectomy, and the collected data included age, PSA level, body weight, BMI, and pathology results. RESULTS: A total of 174 patients diagnosed with adenocarcinoma of the prostate by needle biopsy, and most (N=165) were considered to have localized disease on preoperative multi-parameter magnetic resoanace imaging. After prostatectomy, 73% (N=127) of the patients remained in the localized disease group (group A) and 27%(N=47) of the patients were reclassified to the locally advanced prostate cancer (group B). The value of PSA was higher in Group B (16.9 vs 11.2 ng/dL; p= 0.062), but there was no statistically significant difference between the two groups. After using the numerical values of PSA x body weight and PSA x BMI, a statistically significant difference emerged between the two groups (p= 0.0198 in PSA × BW; p=0.0110 in PSA × BMI). CONCLUSION: The Body mass weighted PSA levels, instead of the traditional PSA concentration, may be better markers for predicting non-organ-confined disease after surgery. It may also be useful in screening and risk categorization.

Sarcopenic obesity in nursing home residents: a multi-center study on diagnostic methods and their association with instrumental activities of daily living.

BACKGROUND: Sarcopenic obesity (SO) in nursing home residents is rarely studied. We aimed to evaluate and compare the prevalence and consistency of different SO diagnostic methods and to investigate which criterion demonstrated a stronger association with instrumental activities of daily living (IADL) disability. METHODS: We consecutively recruited older adults aged ≥ 60 years, residing in 15 nursing homes in Zigong City, China. Sarcopenia obesity was defined according to the European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity criteria (SOESPEN), recommending skeletal muscle mass (SMM) adjusted by body weight (SMM/W) to identify low muscle mass. Further, we adapted ESPEN criteria (SOESPEN-M) by employing SMM adjusted by body mass index (SMM/BMI). RESULTS: We included 832 participants (median age 73.0 years, 296 women). The prevalence of SOESPEN and SOESPEN-M was 43.5% and 45.3%, respectively. SOESPEN showed good consistency with SOESPEN-M (Cohen's kappa = 0.759). More than one-third of participants in the normal weight group were diagnosed with SOESPEN or SOESPEN-M. Even within the underweight group, the prevalence of SOESPEN and SOESPEN-M was 8.9% and 22.2%, respectively. Participants with IADL disability had significantly lower SMM/W and SMM/BMI, but higher fat mass percentage of body weight (FM%) than participants without IADL disability. After full adjustment for potential confounders, SOESPEN-M (OR 1.68, 95% CI 1.21 to 2.32), but not SOESPEN (OR 1.28, 95% CI 0.93 to 1.75), remained significantly associated with IADL disability. CONCLUSIONS: Both SOESPEN and SOESPEN-M showed a high prevalence among nursing home residents, even among individuals with underweight or normal weight. While SOESPEN had a good consistency with SOESPEN-M, only SOESPEN-M was independently associated with IADL disability. Screening and diagnosis of SO should be conducted in nursing home residents irrespective of BMI.

Association between PM2.5 constituents and cardiometabolic risk factors: Exploring individual and combined effects, and mediating inflammation.

BACKGROUND: The individual and combined effects of PM2.5 constituents on cardiometabolic risk factors are sparsely investigated. Besides, the key cardiometabolic risk factor that PM2.5 constituents targeted and the biological mechanisms remain unclear. METHOD: A multistage, stratified cluster sampling survey was conducted in two typically air-polluted Chinese cities. The PM2.5 and its constituents including sulfate, nitrate, ammonium, organic matter, and black carbon were predicted using a machine learning model. Twenty biomarkers in three category were simultaneously adopted as cardiometabolic risk factors. We explored the individual and mixture association of long-term PM2.5 constituents with these markers using generalized additive model and quantile-based g-computation, respectively. To minimize potential confounding effects, we accounted for covariates including demographic, lifestyle, meteorological, temporal trends, and disease-related information. We further used ROC curve and mediation analysis to identify the key subclinical indicators and explore whether inflammatory mediators mediate such association, respectively. RESULT: PM2.5 constituents was positively correlated with HOMA-B, TC, TG, LDL-C and LCI, and negatively correlated with PP and RC. Further, PM2.5 constituent mixture was positive associated with DBP, MAP, HbA1c, HOMA-B, AC, CRI-1 and CRI-2, and negative associated with PP and HDL-C. The ROC analysis further reveals that multiple cardiometabolic risk factors can collectively discriminate exposure to PM2.5 constituents (AUC>0.9), among which PP and CRI-2 as individual indicators exhibit better identifiable performance for nitrate and ammonium (AUC>0.75). We also found that multiple blood lipid indicators may be affected by PM2.5 and its constituents, possibly mediated through complement C3 or hsCRP. CONCLUSION: Our study suggested associations of individual and combined PM2.5 constituents exposure with cardiometabolic risk factors. PP and CRI-2 were the targeted markers of long-term exposure to nitrate and ammonium. Inflammation may serve as a mediating factor between PM2.5 constituents and dyslipidemia, which enhance current understanding of potential pathways for PM2.5-induced preclinical cardiovascular responses.

Incorporation of Finasteride-Loaded Microspheres into Personalized Microneedle for Sustained Transdermal Delivery.

Although finasteride (FNS) tablets are considered the most effective drug for the treatment of androgenetic alopecia (AGA), their clinical applications are limited due to the associated side effects including decreased libido, breast enlargement, and liver dysfunction. In this study, we have developed a personalized microneedle (PMN) with a double-layer structure that incorporates FNS-loaded microspheres (MPs) to accommodate irregular skin surfaces. This design enables the sustained release of FNS, thereby reducing potential side effects. The needle body was synthesized with high-strength hyaluronic acid (HA) as the base material substrate. The backing layer utilized methacrylate gelatin (GelMA) with specific toughness, enabling PMN to penetrate the skin while adapting to various skin environments. The length of PMN needles (10 × 10) was approximately 600 µm, with the bottom of the needles measuring about 330 µm × 330 µm. The distance between adjacent tips was around 600 µm, allowing the drug to penetrate the stratum corneum of the skin. The results of the drug release investigation indicated the sustained and regulated release of FNS from PMN, as compared to that of pure FNS and FNS-MPs. Further, the cytotoxicity assay demonstrates that PMS displays good cytocompatibility. Altogether, this mode of administration has immense potential for the development of delivery of other drugs, as well as in the medical field.

Generation of a Human Induced Pluripotent Stem Cell Line Expressing a Magnetic Resonance Imaging Reporter Gene.

The objective of the current study is to develop a new method for tracking transplanted human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) using magnetic resonance imaging (MRI). The CRISPR/dCas9 activation system is employed to overexpress ferritin heavy chain (FHC) in hiPSC-CMs. The mRNA and protein expression of FHC in hiPSC and hiPSC-CMs significantly increased after transfection. Iron chloride does not affect the cell viability in a concentration range from 0 to 2000 µm. hiPSCs overexpressing FHC (hiPSC- FHCOE) and hiPSC-CMs overexpressing FHC (hiPSC-CM-FHCOE) significantly enhanced cellular uptake of iron chloride but with no changes in electrophysiological properties compared to hiPSC-CM-Control. Furthermore, hiPSC-CM-FHCOE presented robust contrast and lower T2* values, signifying their potential as highly effective candidates for cardiac MRI. Next, hiPSC-CM-FHCOE is injected into mouse hearts and after 3 days of transplantation, MR images are obtained. hiPSC-CM-FHCOE cells exhibited clear signals in the hearts with lower T2* and rapid signal decay. Collectively, data from this proof-of-concept study demonstrated that endogenous labeling with FHC in hiPSC-CMs can be a potent strategy for enhancing the accuracy of cardiac MRI. This technology represents a significant step forward in tracking the transplanted hiPSC-CMs in the hearts of live animals.

Unitig-centered pan-genome machine learning approach for predicting antibiotic resistance and discovering novel resistance genes in bacterial strains.

In current genomic research, the widely used methods for predicting antimicrobial resistance (AMR) often rely on prior knowledge of known AMR genes or reference genomes. However, these methods have limitations, potentially resulting in imprecise predictions owing to incomplete coverage of AMR mechanisms and genetic variations. To overcome these limitations, we propose a pan-genome-based machine learning approach to advance our understanding of AMR gene repertoires and uncover possible feature sets for precise AMR classification. By building compacted de Brujin graphs (cDBGs) from thousands of genomes and collecting the presence/absence patterns of unique sequences (unitigs) for Pseudomonas aeruginosa, we determined that using machine learning models on unitig-centered pan-genomes showed significant promise for accurately predicting the antibiotic resistance or susceptibility of microbial strains. Applying a feature-selection-based machine learning algorithm led to satisfactory predictive performance for the training dataset (with an area under the receiver operating characteristic curve (AUC) of > 0.929) and an independent validation dataset (AUC, approximately 0.77). Furthermore, the selected unitigs revealed previously unidentified resistance genes, allowing for the expansion of the resistance gene repertoire to those that have not previously been described in the literature on antibiotic resistance. These results demonstrate that our proposed unitig-based pan-genome feature set was effective in constructing machine learning predictors that could accurately identify AMR pathogens. Gene sets extracted using this approach may offer valuable insights into expanding known AMR genes and forming new hypotheses to uncover the underlying mechanisms of bacterial AMR.

The antipyretic effect of the famous classical formula Qingwanzi Pills on a rabbit model and its serum metabolomic study.

Qingwanzi Pills (QP) were first mentioned in the "Puji Fang" of the Ming Dynasty, with a history of approximately 600 years. The formula consisted of Gypsum Fibrosum and Indigo Naturalis. It is a famous classical formula with antipyretic effects frequently utilized in ancient China, although our knowledge about the overall antipyretic mechanism of QP remains limited. Therefore, we replicated the fever model in New Zealand rabbits induced by lipopolysaccharide, performed the pharmacodynamic evaluation of QP, identified the differential metabolites among QP groups, and performed pathway enrichment analysis to comparatively analyze the effects of QP on fever-related metabolic pathways by ultra-performance liquid chromatography-mass spectrometry. The results showed that the antipyretic effect of QP was superior to that of each disassembled prescription, with Gypsum Fibrosum primarily contributing to the efficacy, followed by Indigo Naturalis and Junci Medulla. QP had an effective antipyretic effect, which was related to lowering the levels of TNF-α, IL-6, IL-1ß, and calcium in rabbit serum, lowering the levels of PGE2 and cAMP in rabbit cerebrospinal fluid, and increasing the level of calcium in rabbit cerebrospinal fluid. A total of 27 endogenous biomarkers were screened by serum metabolomics for the treatment of fever with QP. It is hypothesized that the antipyretic mechanism of QP may be related to regulating α-linolenic acid, sphingolipid, tryptophan, and bile acid metabolism. In summary, QP exhibited a significant antipyretic effect in rabbits with lipopolysaccharide-induced fever.

Combining anodic alcohol oxidative coupling for C-C bond formation with cathodic ammonia production.

Electrocatalytic oxidation of alcohols using heterogeneous catalysts is a promising aqueous, energy-efficient and environmentally friendly approach, especially for coupling different alcohols to prolong the carbon chain via co-oxidation. Precisely regulating critical steps to tailor electrode materials and electrolyte composition is key to selectively coupling alcohols for targeted synthesis. However, selectively coupling different alcohols remains challenging due to the lack of effective catalyst and electrolyte design promoting specific pathways. Herein, we demonstrate a paired electrolysis strategy for combining anodic oxidative coupling of ethanol (EtOH) and benzyl alcohol (PhCH2OH) to synthesize cinnamaldehyde (CAL) and cathodic ammonia production. The strategies involve: (i) utilizing the salt-out effect to balance selective oxidation and coupling rates; (ii) developing platinum-loaded nickel hydroxide electrocatalysts to accelerate intermediate coupling kinetics; (iii) introducing thermodynamically favorable nitrate reduction at the cathode to improve coupling selectivity by avoiding hydrogenation of products while generating valuable ammonia instead of hydrogen. We achieved 85% coupling selectivity and 278 µmol/h NH3 productive rate at 100 mA/cm2 with a low energy input (∼1.63 V). The membrane-free, low energy, scalable approach with a wide substrate scope highlights promising applications of this methodology. This work advances heterogeneous electrocatalytic synthesis through rational design principles that integrate anodic oxidative coupling with cathodic nitrate reduction reactions, having synergistic effects on efficiency and selectivity.

Wood-inspired anisotropic hydrogel electrolyte with large modulus and low tortuosity realizing durable dendrite-free zinc-ion batteries.

While aqueous zinc-ion batteries exhibit great potential, their performance is impeded by zinc dendrites. Existing literature has proposed the use of hydrogel electrolytes to ameliorate this issue. Nevertheless, the mechanical attributes of hydrogel electrolytes, particularly their modulus, are suboptimal, primarily ascribed to the substantial water content. This drawback would severely restrict the dendrite-inhibiting efficacy, especially under large mass loadings of active materials. Inspired by the structural characteristics of wood, this study endeavors to fabricate the anisotropic carboxymethyl cellulose hydrogel electrolyte through directional freezing, salting-out effect, and compression reinforcement, aiming to maximize the modulus along the direction perpendicular to the electrode surface. The heightened modulus concurrently serves to suppress the vertical deposition of the intermediate product at the cathode. Meanwhile, the oriented channels with low tortuosity enabled by the anisotropic structure are beneficial to the ionic transport between the anode and cathode. Comparative analysis with an isotropic hydrogel sample reveals a marked enhancement in both modulus and ionic conductivity in the anisotropic hydrogel. This enhancement contributes to significantly improved zinc stripping/plating reversibility and mitigated electrochemical polarization. Additionally, a durable quasi-solid-state Zn//MnO2 battery with noteworthy volumetric energy density is realized. This study offers unique perspectives for designing hydrogel electrolytes and augmenting battery performance.

Study on the effects of toosendanin against Eimeria tenella and its impact on the apoptosis of cecal cells in chicks.

To investigate the therapeutic effect of toosendanin (TSN) against Eimeria tenella (E. tenella) in chicks. In this experiment, a chick model of artificially induced E. tenella infection was established. The anti-coccidial effect was investigated by treating different doses of TSN. A preliminary mechanism of action was conducted, using cecal cell apoptosis as a starting point. TSN at the concentration of 5 mg/kg BW showed the best effect against E. tenella with the ACI value of 164.35. In addition, TSN reduced pathological damage to cecal tissue, increased the secretion of glycogen and mucus in cecal mucosa, and enhanced the mucosal protective effect. It also elevated the levels of IFN-γ, IL-2, and IgG in serum, and raised the sIgA content in cecal tissue of infected chicks, thereby improving overall immune function. TSN was observed to promote the apoptosis of cecum tissue cells by TUNEL staining analysis. Immunohistochemistry analysis revealed that in TSN-treated groups, the expression of Caspase-3 and Bax was elevated, while the expression of Bcl-2 was reduced. TSN induced apoptosis in host cells by dose-dependently decreasing the Bcl-2/Bax ratio and upregulating Caspase-3 expression. In summary, TSN exhibited significant anticoccidial efficacy by facilitating apoptosis in host cecal cells, with the most pronounced effect observed at a dosage of 5 mg/kg body weight.

CD4+CD57+ senescent T cells as promoters of systemic lupus erythematosus pathogenesis and the therapeutic potential of senolytic BCL-2 inhibitor.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by persistent activation of immune cells and overproduction of autoantibodies. The accumulation of senescent T and B cells has been observed in SLE and other immune-mediated diseases. However, the exact mechanistic pathways contributing to this process in SLE remain incompletely understood. In this study, we found that in SLE patients: (1) the frequency of CD4+CD57+ senescent T cells was significantly elevated and positively correlated with disease activity; (2) the expression levels of B-lymphoma-2 (BCL-2) family and interferon-induced genes (ISGs) were significantly upregulated; and (3) in vitro, the cytokine IL-15 stimulation increased the frequency of senescent CD4+ T cells and upregulated the expression of BCL-2 family and ISGs. Further, treatment with ABT-263 (a senolytic BCL-2 inhibitor) in MRL/lpr mice resulted in decreased: (1) frequency of CD4+CD44hiCD62L-PD-1+CD153+ senescent CD4+ T cells; (2) frequency of CD19+CD11c+T-bet+ age-related B cells; (3) level of serum antinuclear antibody; (4) proteinuria; (5) frequency of Tfh cells; and (6) renal histopathological abnormalities. Collectively, these results indicated a dominant role for CD4+CD57+ senescent CD4+ T cells in the pathogenesis of SLE and senolytic BCL-2 inhibitor ABT-263 may be the potential treatment in ameliorating lupus phenotypes.