A Randomized, Double-Blind, Parallel-Group Phase I Study Comparing the Pharmacokinetics, Safety, and Immunogenicity of CMAB015, a Candidate Secukinumab Biosimilar, with Its Reference Product Cosentyx® in Healthy Chinese Male Subjects.

Purpose: Secukinumab, a monoclonal antibody targeting interleukin (IL)-17A, is approved for the treatment of psoriasis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, enthesitis-related arthritis, and hidradenitis suppurativa. This study compared the pharmacokinetics (PK), safety, and immunogenicity of CMAB015, a candidate secukinumab biosimilar, with the reference product secukinumab (Cosentyx®) in healthy Chinese male subjects. Patients and methods: This double-blind, parallel-group study randomized healthy Chinese male subjects (N=130) to receive either a single dose of 150 mg CMAB015 or secukinumab subcutaneously. Primary study endpoints were PK parameters such as the maximum concentration (Cmax) and area under the curve from zero to infinity (AUC0-inf), while safety and immunogenicity were secondary endpoints. Results: The 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) of Cmax and AUC0-inf for CMAB015 to secukinumab were all within the bioequivalence limits (80.00-125.00%). Other PK parameters were comparable between the groups. The safety profile of CMAB015 was similar to that of secukinumab, with no serious adverse events related to treatment. The incidence of TEAEs was slightly higher in the CMAB015 group, but these events were mild to moderate in severity and did not lead to any withdrawals from the study. Immunogenicity analysis revealed low rates of anti-drug antibody (ADA) positivity, with similar rates between CMAB015 and secukinumab. Conclusion: This study demonstrated equivalent PK, comparable safety, and immunogenicity of CMAB015 to secukinumab in healthy Chinese male subjects. These findings support further clinical evaluation of CMAB015 as a secukinumab biosimilar. Trial Registration: The trial was registered on Clinicaltrials.gov (Identifier No. NCT05734482) and Chinadrugtrials.org.cn (Identifier No. CTR20230105).

Association of circulating visfatin level and metabolic fatty liver disease: An updated meta-analysis and systematic review.

BACKGROUND: The rate of incidence of metabolic dysfunction-related fatty liver disease (MAFLD) has rapidly increased globally in recent years, but early diagnosis is still a challenge. The purpose of this systematic review and meta-analysis is to identify visfatin for early diagnosis of MAFLD. METHODS: We strictly adhered to the relevant requirements of Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The systematic search was conducted in 7 sources (PubMed, Embase, Cochrane Library, CNKI, Wanfang, CBM, and ClinicalTrials.gov) until February 2024. The meta-analysis was performed using Stata 12. Outcomes were expressed in the form of standardized mean difference (SMD) and 95% confidence interval and were analyzed using meta-analysis. RESULTS: The results showed that there was no significant difference in circulating visfatin levels between patients with MAFLD and controls (SMD = 0.13 [-0.34, 0.60]). However, the outcomes indicated that the level of circulating visfatin was significantly higher in MAFLD patients in the Middle Eastern subgroup (SMD = 0.45 [0.05, 0.85]) and in the obese patient subgroup (SMD = 1.05 [0.18, 1.92]). No publication bias was detected, and sensitivity analysis confirmed the stability of the outcomes. CONCLUSION: The serum visfatin levels of MAFLD patients did not differ significantly from those of controls. However, visfatin concentrations in serum were statistically higher within Middle Eastern or obese MAFLD patients compared to controls. There is a need for further research to investigate visfatin's potential as a biomarker for MAFLD.

[Effects of Film Mulching on Soil Quality, Garlic Yield, and Garlic Quality].

To determine the optimal film management technique for garlic planting, this study aimed to investigate the effects of various film cover methods on soil quality and garlic yield in garlic cropping systems. To achieve these goals, trials with different film cover methods were conducted at the Jiangsu Academy of Agricultural Sciences in Nanjing. To investigate the impact of changes in soil quality and garlic yield, we set up four treatments： no film treatment （CK）, black polyethylene film treatment （HPE）, black poly（butylene- adipate-co-terephthalate） （PBAT） with straw composite film treatment （HSJ）, and white PBAT film treatment （BJ） in a garlic cropping system. Our results indicated that specific mulch coverings had a positive effect on both soil quality and garlic yield. The film cover treatments resulted in significant changes in soil physicochemical properties and bacterial and fungal biomasses and indirectly improved soil quality. Compared to that under the no film treatment, the BJ treatment boosted soil quality by 70%, with the most significant impact, followed by that under the HPE and HSJ treatments, with improvements of 52% and 36%. Random forest modeling indicated that soil organic matter and total nitrogen were the most important factors influencing soil quality. The different film covers significantly increased the diameter of garlic bulbs and single quality. The HSJ treatment exhibited the most significant increase in garlic yield, with 46%, 19%, and 6% improvement compared to that in the CK, HPE, and BJ treatments, respectively. Correlation analysis showed that soil quality under film cover was significantly correlated with the starch content of garlic bulbs, garlic diameter, and single quality. This study highlights that selecting the appropriate mulch film aids in the production of garlic and helps to develop farmland that produces both high-quality and high-yield crops.

[Differential effects of Qingqiao and Laoqiao on bleomycin-induced pulmonary fibrosis in mice by principal component analysis].

The mechanism of alleviating bleomycin-induced pulmonary fibrosis in mice was compared between Qingqiao(Forsythiae Fructus produced with immature fruits) and Laoqiao(Forsythiae Fructus produced with mature fruits) from the pharmacodynamic correlation and composition differences. Mice were randomized into normal, model, pirfenidone(50 mg·kg~(-1)), low-and high-dose(1.3, 2.6 g·kg~(-1), respectively) Qingqiao, and low-and high-dose(1.3, 2.6 g·kg~(-1), respectively) Laoqiao groups. The mouse model of pulmonary fibrosis was established by intratracheal instillation of bleomycin, during which the survival rate and body weight changes of the mice were measured. After modeling, the lung index was calculated, and the pathological changes in the lung tissue were evaluated by hematoxylin-eosin(HE), Masson, and Sirius red staining. Transmission electron microscopy was employed to observe the ultrastructure of the lung tissue. The biochemical assay was employed to measure the levels of transforming growth factor-ß1(TGF-ß1), α-smooth muscle actin(α-SMA), E-cadherin, and hydroxyproline(HYP) in the lung tissue and interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in the bronchoalveolar lavage fluid(BALF). The mRNA and protein levels of matrix metalloproteinase 7(MMP7), collagen Ⅰ, E-cadherin, TNF-α, vimentin, TGF-ß1, and α-SMA in the lung tissue were determined by RT-qPCR and Western blot, respectively. The expression of α-SMA in the lung tissue was detected by the immunofluorescence assay. Principal component analysis was performed to compare the effects of Qingqiao and Laoqiao in ameliorating pulmonary fibrosis. Molecular docking was employed to analyze the binding between the compounds with high content in Laoqiao and TGF-ß1. The cell-counting kit(CCK-8) assay was used to examine the effects of the active compounds on TGF-ß1-induced BEAS-2B and HFL1 cell models. The results showed that Qingqiao and Laoqiao increased the survival rate, reduced the lung index, alleviated the pathological damage and collagen deposition in the lung tissue, ameliorated the damage of lamellar bodies in alveolar epithelial type Ⅱ cells, lowered the level of IL-6 and TNF-α in the BALF, down-regulated the expression of HYP, MMP7, vimentin, collagen Ⅰ, TGF-ß1, and α-SMA, and up-regulated the expression of E-cadherin in the lung tissue of the mouse model of pulmonary fibrosis. The collagen deposition in the mouse model of pulmonary fibrosis was comprehensively evaluated by principal component analysis, and the effects of different treatments followed the trend of high-dose Laoqiao>low-dose Laoqiao>high-dose Qingqiao>low-dose Qingqiao. Molecular docking showed that hydroxytyrosol, caffeic acid, phillygenin, and(-)-lariciresinol had strong binding affinity with TGF-ß1 receptor. The results of cell experiments showed that these compounds significantly attenuated the TGF-ß1-induced damage in BEAS-2B cells and inhibited the TGF-ß1-induced proliferation of HFL1 cells. In conclusion, both Qingqiao and Laoqiao were effective in ameliorating bleomycin-induced pulmonary fibrosis in mice. Laoqiao was superior to Qingqiao in reducing collagen deposition, which might be attributed to the higher content of hydroxytyrosol, caffeic acid, phillygenin, and(-)-lariciresinol in Laoqiao than in Qingqiao.

[Risk factors and prognosis of pediatric silent lupus nephritis with class â ¢ to â ¤]. / 儿童⠢~â ¤åž‹æ— ç—‡çŠ¶æ€§ç‹¼ç–®æ€§è‚¾ç‚Žçš„å±é™©å› ç´ åŠé¢„åŽåˆ†æž.

OBJECTIVES: To study the risk factors and prognostic characteristics of pediatric silent lupus nephritis (SLN) with class Ⅲ to V. METHODS: A retrospective study was conducted to collect clinical data from 30 children diagnosed with SLN at the Department of Pediatrics, Second Xiangya Hospital, Central South University, from May 2007 to April 2023. Based on renal pathological classification, the patients were divided into a class Ⅱ group (12 cases) and a class Ⅲ to Ⅴ group (18 cases). The risk factors for the occurrence of class Ⅲ to Ⅴ SLN were analyzed, and the prognostic characteristics were summarized. RESULTS: Among the 30 SLN patients, the median follow-up time was 61.50 months. There were no statistically significant differences in the proportions of patients who discontinued glucocorticoids or achieved low disease activity status, nor in the annual decline rate of estimated glomerular filtration rate (eGFR) between the class Ⅱ and class Ⅲ to V groups (P>0.05). However, three patients in the class Ⅱ group progressed to stage 1 chronic kidney disease (CKD), while eight patients in the class III to V group reached stage 1 CKD, and four patients reached stage 2 CKD. Among the 26 female SLN patients, serum complement C3 levels in the class III to V group were lower than those in the class Ⅱ group (P<0.05). Serum C3 levels in SLN patients, as well as in female SLN patients, were negatively correlated with the fluorescence intensity of IgA, IgG, and C3 immune complexes in the kidneys (P<0.05). Additionally, serum C3 levels in female SLN patients were negatively correlated with the renal pathological activity index (P<0.05). Binary logistic regression analysis indicated that being female and having low serum complement C3 levels were risk factors for the occurrence of class Ⅲ to V SLN in children (P<0.05). CONCLUSIONS: Class Ⅲ to V SLN is not uncommon among SLN children, and there remains a risk of long-term renal function progression. Being female and having low serum complement C3 levels are identified as risk factors for class Ⅲ to V SLN in children.

A biomimetic upconversion nanoreactors for near-infrared driven H2 release to inhibit tauopathy in Alzheimer's disease therapy.

Abnormal hyperphosphorylation of tau protein is a principal pathological hallmark in the onset of neurodegenerative disorders, such as Alzheimer's disease (AD), which can be induced by an excess of reactive oxygen species (ROS). As an antioxidant, hydrogen gas (H2) has the potential to mitigate AD by scavenging highly harmful ROS such as •OH. However, conventional administration methods of H2 face significant challenges in controlling H2 release on demand and fail to achieve effective accumulation at lesion sites. Herein, we report artificial nanoreactors that mimic natural photosynthesis to realize near-infrared (NIR) light-driven photocatalytic H2 evolution in situ. The nanoreactors are constructed by biocompatible crosslinked vesicles (CVs) encapsulating ascorbic acid and two photosensitizers, chlorophyll a (Chla) and indoline dye (Ind). In addition, platinum nanoparticles (Pt NPs) serve as photocatalysts and upconversion nanoparticles (UCNP) act as light-harvesting antennas in the nanoreacting system, and both attach to the surface of CVs. Under NIR irradiation, the nanoreactors release H2 in situ to scavenge local excess ROS and attenuate tau hyperphosphorylation in the AD mice model. Such NIR-triggered nanoreactors provide a proof-of-concept design for the great potential of hydrogen therapy against AD.

Age-related changes of node degree in the multiple-demand network predict fluid intelligence.

Fluid intelligence is an individual's innate ability to cope with complex situations and is gradually reduced across adults aging. The realization of fluid intelligence requires the simultaneous activity of multiple brain regions and depends on the structural connection of distributed brain regions. Uncovering the structural features of brain connections associated with fluid intelligence decline will provide reference for the development of intervention and treatment programs for cognitive decline. Using structural magnetic resonance imaging data of 454 healthy participants (18-87 years) from the Cam-CAN dataset, we constructed structural similarity network for each participant and calculated the node degree. Spearman correlation analysis showed that age was positively correlated with degree centrality in the cingulate cortex, left insula and subcortical regions, while negatively correlated with that in the orbito-frontal cortex, right middle temporal and precentral regions. Partial least squares (PLS) regression showed that the first PLS components explained 32 % (second PLS component: 20 %, p perm < 0.001) of the variance in fluid intelligence. Additionally, the degree centralities of anterior insula, supplementary motor area, prefrontal, orbito-frontal and anterior cingulate cortices, which are critical nodes of the multiple-demand network (MDN), were linked to fluid intelligence. Increased degree centrality in anterior cingulate cortex and left insula partially mediated age-related decline in fluid intelligence. Collectively, these findings suggest that the structural stability of MDN might contribute to the maintenance of fluid intelligence.

Legacy sources determine current water quality: Nitrogen and phosphorus in streams of Australia, China, Sweden and USA.

Waterborne nutrient loads to downstream ecosystems integrate contributions from both active and legacy sources. Effective mitigation of nutrient pollution and eutrophication around the world requires distinction of these, largely unknown, relative load contributions. Here, the active and legacy contributions to nitrogen and phosphorus loads are distinguished in numerous streams and associated hydrological catchments of Australia, China, Sweden, and USA. The legacy contributions overshadow the active ones in all countries during 2005-2020. China and USA, with higher population densities and related overall human-activity levels, also have substantial active contributions. The median values of legacy concentration contributions of total nitrogen range from 321 (in Sweden) to 1850 µg/L (in USA); whereas the active contributions range from 2.2 (in Australia) to 315 µg/L (in USA). In China, nitrogen data are available only for ammonia, with median concentration contributions of 294 µg/L for legacy and 352 µg/L for active sources. For total phosphorus, the median values of legacy concentration contributions range from 28.8 (in Sweden) to 270 µg/L (in USA), while the active ones range from 0.1 (in Australia) to 67.3 µg/L (in USA). For relatively fast mitigation responses, China and USA need to mitigate their current nutrient emissions, while Australia and Sweden need a shift in mitigation focus to targeting their dominant legacy source contributions. The data-driven method testing in this study supports the used source distinction-attribution approach. This enables consistent source identification and tailoring of targeted measures for effective nutrient load mitigation in various regional contexts.

Erratum to: Aberrant dynamic functional connectivity of thalamocortical circuitry in major depressive disorder.

The online version of the original article can be found at https://doi.org/10.1631/jzus.B2300401.

The role of cholesterol metabolism in lung cancer.

Elevated serum cholesterol metabolism is associated with a reduced risk of lung cancer. Disrupted cholesterol metabolism is evident in both lung cancer patients and tumor cells. Inhibiting tumor cell cholesterol uptake or biosynthesis pathways, through the modulation of receptors and enzymes such as liver X receptor and sterol-regulatory element binding protein 2, effectively restrains lung tumor growth. Similarly, promoting cholesterol excretion yields comparable effects. Cholesterol metabolites, including oxysterols and isoprenoids, play a crucial role in regulating cholesterol metabolism within tumor cells, consequently impacting cancer progression. In lung cancer patients, both the cholesterol levels in the tumor microenvironment and within tumor cells significantly influence cell growth, proliferation, and metastasis. The effects of cholesterol metabolism are further mediated by the reprogramming of immune cells such as T cells, B cells, macrophages, myeloid-derived suppressor cells, among others. Ongoing research is investigating drugs targeting cholesterol metabolism for clinical treatments. Statins, targeting the cholesterol biosynthesis pathway, are widely employed in lung cancer treatment, either as standalone agents or in combination with other drugs. Additionally, drugs focusing on cholesterol transportation have shown promise as effective therapies for lung cancer. In this review, we summarized current research regarding the rule of cholesterol metabolism and therapeutic advances in lung cancer.

Getting to Know the Effect Theory of Traditional Pediatric Tuina in the View of Modern Medicine in Three Minor Perspectives.

Pediatric tuina is a traditional Chinese medicine (TCM) modality that is well-accepted and applied in China currently. As a traditional medicine, it is based on TCM theories and clinical experience. In the TCM area, the "self-healing" system of the human body includes two aspects: self-regulation and adaptation, through which pediatric tuina could rectify dysfunctional states and guide the transition back to homeostasis. Pediatric tuina manipulations sufficiently, specifically, and accurately simulate certain sensory receptors in the skin, which in turn activates the internal self-healing function of the human body. We summarized the main opinions on pediatric tuina mechanism in ancient literature into three minor perspectives and demonstrated them by combining them with modern medical knowledge. First, children at a young age are more responsive to stimulations on the skin surface; second, the sensory receptors and pediatric tuina acupoints on the skin surface have a similar distribution pattern; third, the specific manipulations of pediatric tuina provide multiple stimuli that are detected by a variety of surface sensory receptors for information collection. Each point could be tested via clinical trials with appropriate-designed comparisons.

Construction of an extubation protocol for adult tracheal intubation patients in the intensive care unit: A Delphi study.

OBJECTIVE: The objective of this study was to develop an extubation practice protocol for adult intensive care unit (ICU) patients who underwent endotracheal intubation, providing theoretical guidance for clinical extubation procedures in the ICU. METHODS: A research team was established consisting of medical, nursing, anaesthesia, and respiratory therapy professionals; the multidisciplinary team systematically searched domestic and foreign literature, summarised the best evidence, and combined it with clinical practice experience to preliminarily develop an extubation protocol for adult ICU patients who underwent endotracheal intubation. Seventeen experts in critical care medicine, intensive care nursing, clinical anaesthesia, and respiratory therapy were invited to participate in a Delphi expert consultation to screen and modify the draft protocol. RESULTS: The response rates of the two Delphi expert enquiries were 100% and 94.1%, with expert authority coefficients of 0.94 and 0.93, respectively, and Kendall's concordance coefficients were 0.152 and 0.198, respectively, indicating statistically significant differences (p < 0.001). The final protocol included three level I indicators, 14 level II indicators, and 34 level III indicators, covering extubation evaluation, implementation, and postextubation management. CONCLUSION: The extubation protocol for adult tracheal intubation patients in the ICU constructed in this study is scientific, practical, and reliable. This study can provide theoretical guidance for extubation in ICU patients who have undergone endotracheal intubation.

Elevated ALT/AST ratio as a marker for NAFLD risk and severity: insights from a cross-sectional analysis in the United States.

Background: The prevalence and incidence of Nonalcoholic fatty liver disease (NAFLD) are increasing worldwide, and NAFLD has emerged as a prominent global health concern. The link between serum alanine aminotransferase (ALT) to aspartate aminotransferase (AST) ratio and NAFLD remains unclear. This study investigated the association between the ALT/AST ratio and NAFLD prevalence, including liver steatosis and fibrosis levels in the population. Methods: We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018, including 4753 participants. Subgroup analyses, stratified by age, gender, and body mass index (BMI), were performed, along with adjusted multivariable logistic regression analyses to evaluate the relationship between ALT/AST levels and the likelihood of NAFLD, liver steatosis, and hepatic fibrosis stage. A generalized additive model examined the non-linear relationship between ALT/AST and the probability of developing NAFLD. Results: Among 4753 participants, 1508 (31.73%) were diagnosed with NAFLD. Significant positive correlations between ALT/AST and NAFLD risk were found across all models. In addition, the subgroup analysis by gender, age, and BMI suggested that ALT/AST showed a positive correlation with NAFLD. The ALT/AST ratio was positively correlated with the degree of liver steatosis and liver fibrosis. The correlation between ALT/AST and the incidence of NAFLD showed a non-linear pattern. In women, the non-linear trend is particularly evident, showing an inverted U-shaped curve with an inflection point of 1.302. A receiver operating characteristic (ROC) analysis showed that the predictive value of ALT/AST for NAFLD was better than that of traditional liver enzyme parameters. Conclusion: A higher ALT/AST ratio was independently associated with a significantly higher risk of NAFLD and liver fibrosis within American cohorts. This link is robust among females, children, and adolescents. ALT/AST ratio can be used as a simple and effective noninvasive biomarker to identify individuals with high risk of NAFLD.

Clinical application of prone position to suppress respiratory movement artifacts in supine position during magnetic resonance cholangiopancreatography/MRI.

PURPOSE: To compare the image quality of magnetic resonance cholangiopancreatography (MRCP) in the supine position and prone position under the conditions of the same equipment, the same sequence (3D Navigator Triggered Sampling Perfection with Application-Optimized Contrast Using Different Flip-angle Evolutions, 3D-NT-SPACE) and the same patient, and to explore the clinical application value of prone position in MRCP examination to suppress respiratory motion artifacts. METHODS: 53 participants who underwent MRCP in our hospital from April 2020 to August 2022 were prospectively collected. The 3D-NT-SPACE sequence was used in these patients. The visibility of the common bile duct, common hepatic duct, main pancreatic duct, and first- and second- and third-level branches of the intrahepatic bile duct and the comfort of the participants in two positions were subjective-evaluated. The Signal-to-noise ratio (SNR) and contrast-to-noise ratio were objective-evaluated. Statistical analysis was performed using Shapiro-Wilk, Levene's, Mann Whitney U test, Pearson chi-square test, and one-sample chi-square test. RESULTS: 53 patients (51.92 years ± 2.02, 20 men) were evaluated. There were significant differences in the second- and third-level branches visibility score, the main pancreatic duct visibility score, the image quality score of the pancreaticobiliary tree, the blur and motion artifact score, the total image quality score, and SNR between the two positions (p < 0.05). CONCLUSIONS: The overall image quality of the prone position was better than that of the supine position. The prone position is a useful complement to the supine position.

Pulmonary Hypertension in Hemodialysis Patients and Its Determinants: A Hospital Based Cross-Sectional Study.

Purpose: Pulmonary hypertension (PH) is a serious complication in hemodialysis patients, which is associated with a significantly increased risk of morbidity and mortality. The present study aims to investigate PH frequency and associated factors in patients undergoing maintenance hemodialysis. Patients and Methods: This cross-sectional study was conducted in the hemodialysis department of the Shandong Provincial Third Hospital, China, from January 2016 to December 2022. A total of 167 consecutive patients who underwent regular hemodialysis treatment for at least three months were included in the study. Patients with a systolic pulmonary artery pressure (sPAP) value >35 mmHg at rest were considered to have PH. The relationship between PH and various demographic, laboratory, and echocardiographic parameters was evaluated. Results: A total of 93 patients (55.7%) were diagnosed with PH. Multivariate logistic regression analysis indicated that low serum levels of albumin (OR 0.89, 95% CI 0.82-0.98, p = 0.017), low serum levels of triglycerides (OR 0.32, 95% CI 0.15-0.69, p = 0.003), and high right atrial diameter (OR 1.19, 95% CI 1.04-1.37, p = 0.011) were significantly associated with an increased risk of PH. Conclusion: PH is a common finding in hemodialysis patients and is independently associated with serum levels of albumin, serum levels of triglyceride, and right atrial diameter; this suggests that evaluating these non-invasive and relatively easily available parameters may be useful in identifying patients with a high risk of PH. However, further studies are required to confirm these findings.

Layer Hall Detection of the Néel Vector in Centrosymmetric Magnetoelectric Antiferromagnets.

The efficient detection of the Néel vector in antiferromagnets is one of the prerequisites toward antiferromagnetic spintronic devices and remains a challenging problem. Here, we propose that the layer Hall effect can be used to efficiently detect the Néel vector in centrosymmetric magnetoelectric antiferromagnets. Thanks to the robust surface magnetization of magnetoelectric antiferromagnets, the combination of sizable exchange field and an applied electric field results in the layer-locked spin-polarized band edges. Moreover, the Berry curvature can be engineered efficiently by an electric field, which consequently gives rise to the layer-locked Berry curvature responsible for the layer Hall effect. Importantly, it is demonstrated that the layer Hall conductivity strongly depends on the Néel vector orientation and exhibits rich electromagnetic responses, which can be used to detect the Néel vector reversal. Based on density functional theory calculations, we exemplify those phenomena in the prototypical Cr_{2}O_{3} compound. A complete list of the magnetic point groups sustaining the layer Hall effect is presented, aiding the search for realistic materials. Our work proposes a novel approach to detect the Néel vector and holds great promise for antiferromagnetic spintronic applications.

Sevoflurane anesthesia during late gestation induces cognitive disorder in rat offspring via the TLR4/BDNF/TrkB/CREB pathway.

Sevoflurane (Sevo) is widely used for general anesthesia during pregnancy. Emerging evidence indicates that maternal Sevo exposure can trigger developmental neurotoxicity in the offspring. Nonetheless, the underlying mechanisms need further investigation. Pregnant Sprague-Dawley rats on gestational day 18 were exposed to 3.5% Sevo to induce the rat model of neurotoxicity. TAK-242, a TLR4 inhibitor, was administrated to inhibit the signaling transduction. Hippocampal tissues of rat offspring were harvested for immunohistochemical staining, TUNEL staining, Western blotting, ELISA, and measurement of oxidative stress-related markers. Serum samples were collected to evaluate lipid metabolism-associated factors. Morris water maze was implemented to test the cognitive function of offspring rats. Rat hippocampal neurons were isolated to elucidate the effect of TAK-242 on the BDNF/TrkB/CREB signaling in vitro. The results showed that maternal Sevo exposure during the third trimester induced neuroinflammation, lipid metabolism disturbance, and oxidative stress, and impaired the spatial learning and memory of rat offspring. Sevo upregulated TLR4 and impeded BDNF/TrkB/CREB signaling transduction in the hippocampus of rat offspring; TAK-242 administration reversed these effects. In conclusion, Sevo anesthesia during late gestation impairs the learning and memory ability of rat offspring possibly by promoting neuroinflammation and disturbing lipid metabolism via the TLR4/BDNF/TrkB/CREB pathway.

Screening and modification of (+)-germacrene A synthase for the production of the anti-tumor drug (-)-ß-elemene in engineered Saccharomyces cerevisiae.

(-)-ß-Elemene is a primary bioactive compound derived from Curcuma wenyujin and has been widely utilized as an anti-tumor agent for various types of cancer. Due to the inefficiency of plant extraction methods for ß-elemene, significant efforts have been directed toward the heterogeneous biosynthesis of ß-elemene using microbial cell factories. However, there has been less emphasis on the stereochemical configuration of germacrene A and its rearranged product, ß-elemene. In this study, we constructed a yeast cell factory to produce (-)-ß-elemene by optimizing the mevalonate pathway and screening for germacrene A synthases (GASs) from both plant and microbial sources. Notably, we discovered that the rearranged products of GASs exhibited different conformations, and only (+)-germacrene A produced by plant-derived GASs could rearrange to form (-)-ß-elemene. Building on this discovery, we further investigated the catalytic mechanisms of GASs and developed an efficient catalytic gene module for generating (+)-germacrene A. Ultimately, the engineered yeast produced 1152 mg/L of (-)-ß-elemene, marking the highest titer reported in yeast to date. Overall, this work highlights the differences in the stereoconformations of catalytic products between plant- and microbial-derived germacrene A synthases and establishes a foundation for the green and efficient production of ß-elemene with a specific stereochemical configuration.

Characterization of Limbus Biomechanical Properties Using Optical Coherence Elastography.

The elasticity of the limbus is crucial for ocular health, yet it remains inadequately explored. This study employs acoustic radiation force optical coherence elastography (ARF-OCE) to evaluate the biomechanical properties of the limbus under varying intraocular pressures. The method was validated using a heterogeneous phantom and subsequently applied to ex vivo porcine limbus samples. Elastic wave velocity at specific locations within the limbus was calculated, and the corresponding Young's modulus values were obtained. Spatial elasticity distribution maps were generated by correlating Young's modulus values with their respective locations in the two-dimensional structural images. The results indicate that ARF-OCE enhances the understanding of limbus biomechanical behavior and holds potential for diagnosing regional variations caused by ocular diseases.