A Multiferroic Spin-Crossover Molecular Crystal.

Spin-crossover (SCO) ferroelectrics with dual-function switches have attracted great attention for significant magnetoelectric application prospects. However, the multiferroic crystals with SCO features have rarely been reported. Herein, a molecular multiferroic Fe(II) crystalline complex [FeII(C8-F-pbh)2] (1-F, C8-F-pbh = (1Z,N'E)-3-F-4-(octyloxy)-N'-(pyridin-2-ylmethylene)-benzo-hydrazonate) showing the coexistence of ferroelectricity, ferroelasticity, and SCO behavior is presented for the first time. By H/F substitution, the low phase transition temperature (270 K) of the non-fluorinated parent compound is significantly increased to 318 K in 1-F, which exhibits a spatial symmetry breaking 222F2 type ferroelectric phase transition with clear room-temperature ferroelectricity. Besides, 1-F also displays a spin transition between high- and low-spin states, accompanied by the d-orbital breaking within the t2g 4eg 2 and t2g 6eg° configuration change of octahedrally coordinated FeII center. Moreover, the 222F2 type ferroelectric phase transition is also a ferroelastic one, verified by the ferroelectric domains reversal and the evolution of ferroelastic domains. To the knowledge, 1-F is the first multiferroic SCO molecular crystal. This unprecedented finding sheds light on the exploration of molecular multistability materials for future smart devices.

Neuroprotective Effects of AER-271 in a tMCAO Mouse Model: Modulation of Autophagy, Apoptosis, and Inflammation.

Following ischemic stroke, aquaporin 4 (AQP4) expression modifications have been associated with increased inflammation. However, the underlying mechanisms are not fully understood. This study aims to elucidate the mechanistic basis of post-cerebral ischemia-reperfusion (I/R) inflammation by employing the AQP4-specific inhibitor, AER-271. The middle cerebral artery occlusion (MCAO) model was used to induce ischemic stroke in mice. C57BL/6 mice were randomly allocated into four groups: sham operation, I/R, AER-271, and 2-(nicotinamide)-1,3,4-thiadiazole (TGN-020) treatment, with observations recorded at 1 day, 3 days, and 7 days post-tMCAO. Each group consisted of 15 mice. Procedures included histological examination through HE staining, neurological scoring, Western blot analysis, and immunofluorescence staining. AER-271 treatment yielded significant improvements in post-stroke weight recovery and neurological scores, accompanied by a reduction in cerebral infarction volume. Moreover, AER-271 exhibited a noticeable influence on autophagic and apoptotic pathways, affecting the activation of both pro-inflammatory and anti-inflammatory cytokines. Alterations in the levels of inflammatory biomarkers MCP-1, NLRP3, and caspase 1 were also detected. Finally, a comparative assessment of the effects of AER-271 and TGN-020 in mitigating apoptosis and microglial polarization in ischemic mice revealed neuroprotective effects with no significant difference in efficacy. This study provides essential insights into the neuroprotective mechanisms of AER-271 in cerebral ischemia-reperfusion injury, offering potential clinical applications in the treatment of ischemic cerebrovascular disorders.

Application of metagenomic next-generation sequencing for rapid molecular identification in spinal infection diagnosis.

Objective: This study aimed to determine the sensitivity and specificity of metagenomic next-generation sequencing (mNGS) for detecting pathogens in spinal infections and to identify the differences in the diagnostic performance between mNGS and targeted next-generation sequencing (tNGS). Methods: A total of 76 consecutive patients with suspected spinal infections who underwent mNGS, culture, and histopathological examinations were retrospectively studied. The final diagnosis of the patient was determined by combining the clinical treatment results, pathological examinations, imaging changes and laboratory indicators. The sensitivity and specificity of mNGS and culture were determined. Results: The difference between the two detection rates was statistically significant (p < 0.001), with mNGS exhibiting a significantly higher detection rate (77.6% versus 18.4%). The average diagnosis time of mNGS was significantly shorter than that of bacterial culture (p < 0.001, 1.65 versus 3.07 days). The sensitivity and accuracy of mNGS were significantly higher than that of the culture group (p < 0.001, 82.3% versus 17.5%; 75% versus 27.6%), whereas the specificity of mNGS (42.9%) was lower than that of the culture group (p > 0.05, 42.9% versus 76.9%). The sensitivity, specificity, accuracy, and positive predictive value (PPV) of pus were higher than those of tissue samples for mNGS, whereas for culture, the sensitivity, specificity, accuracy, and PPV of tissue samples were higher than those of pus. tNGS demonstrated higher sensitivity and accuracy in diagnosing tuberculosis (TB) than mNGS (80% versus 50%; 87.5% versus 68.8%). Conclusion: mNGS for spinal infection demonstrated better diagnostic value in developing an antibiotic regimen earlier, and it is recommended to prioritize pus samples for testing through mNGS. Moreover, tNGS outperformed other methods for diagnosing spinal TB and identifying antibiotic-resistance genes in drug-resistant TB.

Evaluating the Impact of an Organic Trace Mineral mix on the Redox Homeostasis, Immunity, and Performance of Sows and their Offspring.

The objective of the study was to evaluate the effects of trace mineral supplementation in sows during gestation and lactation on the performance and health status of sows and their offspring. Sows (n = 30; Landrace × Yorkshire; avg parity = 3.9) were randomly allocated into two dietary treatments. Sows received a basal diet supplemented with 12 mg/kg Cu, 30 mg/kg Fe, 90 mg/kg Zn, 70 mg/kg Mn, 0.30 mg/kg Se, and 1.5 mg/kg I from an inorganic trace mineral source (ITM) or a blend of hydroxychloride and organic trace mineral source (HOTM) from day 1 of gestation until the end of the lactation period at day 21. Compared to the ITM, the HOTM supplementation increased (P < 0.05) both litter birth weight and individual piglet birth weight. Although not statistically significant, HOTM tended to increase (P = 0.069) the level of lactose in colostrum. HOTM increased (P < 0.05) the concentration of Mn and Se in the colostrum, milk, and serum of sows and/or piglets. Notably, the Zn concentration in the serum of sows was higher in sows supplemented with ITM compared to HOTM. Moreover, HOTM increased (P < 0.05) the activities of GPX and SOD in gestating sows and piglets, as well as increased (P < 0.05) cytokines (IL-1ß, TNF-α, and IL-10) in the serum of sows. The immunoglobulins (IgA, IgG, and IgM) also increased in sows and/or piglets at certain experimental time points. In conclusion, HOTM supplementation positively affected piglet development and improved the health status of sows and piglets potentially by regulating redox homeostasis and immunity.

Association of lipid-lowering drugs with risk of sarcopenia: a drug target mendelian randomization study and meta-analysis.

BACKGROUND: Lipid-lowering drugs are widely used among the elderly, with some studies suggesting links to muscle-related symptoms. However, the causality remains uncertain. METHODS: Using the Mendelian randomization (MR) approach, we assessed the causal effects of genetically proxied reduced low-density lipoprotein cholesterol (LDL-C) through inhibitions of hydroxy-methyl-glutaryl-CoA reductase (HMGCR), proprotein convertase subtilisin/kexin type 9 (PCSK9), and Niemann-Pick C1-like 1 (NPC1L1) on sarcopenia-related traits, including low hand grip strength, appendicular lean mass, and usual walking pace. A meta-analysis was conducted to combine the causal estimates from different consortiums. RESULTS: Using LDL-C pooled data predominantly from UK Biobank, genetically proxied inhibition of HMGCR was associated with higher appendicular lean mass (beta = 0.087, P = 7.56 × 10- 5) and slower walking pace (OR = 0.918, P = 6.06 × 10- 9). In contrast, inhibition of PCSK9 may reduce appendicular lean mass (beta = -0.050, P = 1.40 × 10- 3), while inhibition of NPC1L1 showed no causal impact on sarcopenia-related traits. These results were validated using LDL-C data from Global Lipids Genetics Consortium, indicating that HMGCR inhibition may increase appendicular lean mass (beta = 0.066, P = 2.17 × 10- 3) and decelerate walking pace (OR = 0.932, P = 1.43 × 10- 6), whereas PCSK9 inhibition could decrease appendicular lean mass (beta = -0.048, P = 1.69 × 10- 6). Meta-analysis further supported the robustness of these causal associations. CONCLUSIONS: Genetically proxied HMGCR inhibition may increase muscle mass but compromise muscle function, PCSK9 inhibition could result in reduced muscle mass, while NPC1L1 inhibition is not associated with sarcopenia-related traits and this class of drugs may serve as viable alternatives to sarcopenia individuals or those at an elevated risk.

Biodegradable Ferroelectric Molecular Plastic Crystal HOCH2(CF2)7CH2OH Structurally Inspired by Polyvinylidene Fluoride.

Ferroelectric materials, traditionally comprising inorganic ceramics and polymers, are commonly used in medical implantable devices. However, their nondegradable nature often necessitates secondary surgeries for removal. In contrast, ferroelectric molecular crystals have the advantages of easy solution processing, lightweight, and good biocompatibility, which are promising candidates for transient (short-term) implantable devices. Despite these benefits, the discovered biodegradable ferroelectric materials remain limited due to the absence of efficient design strategies. Here, inspired by the polar structure of polyvinylidene fluoride (PVDF), a ferroelectric molecular crystal 1H,1H,9H,9H-perfluoro-1,9-nonanediol (PFND), which undergoes a cubic-to-monoclinic ferroelectric plastic phase transition at 339 K, is discovered. This transition is facilitated by a 2D hydrogen bond network formed through O-H···O interactions among the oriented PFND molecules, which is crucial for the manifestation of ferroelectric properties. In this sense, by reducing the number of -CF2- groups from ≈5 000 in PVDF to seven in PFND, it is demonstrated that this ferroelectric compound only needs simple solution processing while maintaining excellent biosafety, biocompatibility, and biodegradability. This work illuminates the path toward the development of new biodegradable ferroelectric molecular crystals, offering promising avenues for biomedical applications.

Chemo-, regio- and enantioselective hydroformylation of trisubstituted cyclopropenes: access to chiral quaternary cyclopropanes.

Catalytic asymmetric synthesis of polysubstituted chiral cyclopropane presents a significant challenge in organic synthesis due to the difficulty in enantioselective control. Here we report a rhodium-catalyzed highly chemo-, regio- and enantioselective hydroformylation of trisubstituted cyclopropenes affording chiral quaternary cyclopropanes. Importantly, the easy made sterically bulky ligand L1 can effectively suppress hydrogenation and decomposition reactions and give quaternary cyclopropanes with high regio- and enantioselectivities for both aryl and alkyl functionalized substrates. Control experiments and computational studies reveal the sterically hindered well-defined chiral pocket instead of the substrates bearing electron-withdrawing diester groups is important for controlling the enantioselectivity and regioselectivity. Scale-up reaction and follow-up diverse transformations are also presented. Density Functional theory (DFT) computations suggest that the regio- and enantio-selectivities originate from the cyclopropene insertion to the Rh-H bond. The high regioselectivity is found to benefit from the presence of more efficient noncovalent interactions (NCIs) manifesting in the form of C-H···Cl, C-H···N, and l.p(Cl)···π contacts.

Recombinant human thrombopoietin in alleviating endothelial cell injury in sepsis.

Background: To evaluate the effect of recombinant human thrombopoietin (rhTPO) on clinical prognosis by exploring changes in endothelial cell injury markers and inflammatory factors in patients with sepsis after treatment with rhTPO. Methods: This retrospective observational study involved patients with sepsis (diagnosed according to Sepsis 3.0) admitted to Shanghai General Hospital intensive care unit from January 1, 2019 to December 31, 2022. Patients were divided into two groups (control and rhTPO) according to whether they received rhTPO. Baseline information, clinical data, prognosis, and survival status of the patients, as well as inflammatory factors and immune function indicators were collected. The main monitoring indicators were endothelial cell-specific molecule (ESM-1), human heparin-binding protein (HBP), and CD31; secondary monitoring indicators were interleukin (IL)-6, tumor necrosis factor (TNF)-α, extravascular lung water index, platelet, antithrombin III, fibrinogen, and international normalized ratio. We used intraperitoneal injection of lipopolysaccharide (LPS) to establish a mouse model of sepsis. Mice were randomly divided into four groups: normal saline, LPS, LPS + rhTPO, and LPS + rhTPO + LY294002. Plasma indicators in mice were measured by enzyme-linked immunosorbent assay. Results: A total of 84 patients were included in the study. After 7 days of treatment, ESM-1 decreased more significantly in the rhTPO group than in the control group compared with day 1 (median=38.6 [interquartile range, IQR: 7.2 to 67.8] pg/mL vs. median=23.0 [IQR: -15.7 to 51.5] pg/mL, P=0.008). HBP and CD31 also decreased significantly in the rhTPO group compared with the control group (median=59.6 [IQR: -1.9 to 91.9] pg/mL vs. median=2.4 [IQR: -23.2 to 43.2] pg/mL; median=2.4 [IQR: 0.4 to 3.5] pg/mL vs. median=-0.6 [IQR: -2.2 to 0.8] pg/mL, P <0.001). Inflammatory markers IL-6 and TNF-α decreased more significantly in the rhTPO group than in the control group compared with day 1 (median=46.0 [IQR: 15.8 to 99.1] pg/mL vs. median=31.2 [IQR: 19.7 to 171.0] pg/mL, P <0.001; median=17.2 [IQR: 6.4 to 23.2] pg/mL vs. median=0.0 [IQR: 0.0 to 13.8] pg/mL, P=0.010). LPS + rhTPO-treated mice showed significantly lower vascular von Willebrand factor (P=0.003), vascular endothelial growth factor (P=0.002), IL-6 (P <0.001), and TNF-α (P <0.001) than mice in the LPS group. Endothelial cell damage factors vascular von Willebrand factor (P=0.012), vascular endothelial growth factor (P=0.001), IL-6 (P <0.001), and TNF-α (P=0.001) were significantly elevated by inhibiting the PI3K/Akt pathway. Conclusion: rhTPO alleviates endothelial injury and inflammatory indices in sepsis, and may regulate septic endothelial cell injury through the PI3K/Akt pathway.

Autophagy Regulation Attenuates Neuroinflammation and Cognitive Decline in an Alzheimer's Disease Mouse Model with Chronic Cerebral Hypoperfusion.

This study investigates the role of autophagy regulation in modulating neuroinflammation and cognitive function in an Alzheimer's disease (AD) mouse model with chronic cerebral hypoperfusion (CCH). Using the APP23/PS1 mice plus CCH model, we examined the impact of autophagy regulation on cognitive function, neuroinflammation, and autophagic activity. Our results demonstrate significant cognitive impairments in AD mice, exacerbated by CCH, but mitigated by treatment with the autophagy inhibitor 3-methyladenine (3-MA). Dysregulation of autophagy-related proteins, accentuated by CCH, underscores the intricate relationship between cerebral blood flow and autophagy dysfunction in AD pathology. While 3-MA restored autophagic balance, rapamycin (RAPA) treatment did not induce significant changes, suggesting alternative therapeutic approaches are necessary. Dysregulated microglial polarization and neuroinflammation in AD+CCH were linked to cognitive decline, with 3-MA attenuating neuroinflammation. Furthermore, alterations in M2 microglial polarization and the levels of inflammatory markers NLRP3 and MCP1 were observed, with 3-MA treatment exhibiting potential anti-inflammatory effects. Our findings shed light on the crosstalk between autophagy and neuroinflammation in AD+CCH and suggest targeting autophagy as a promising strategy for mitigating neuroinflammation and cognitive decline in AD+CCH.

A Two-color Single-molecule Sequencing Platform and Its Clinical Applications.

DNA sequencers have become increasingly important research and diagnostic tools over the past 20 years. In this study, we developed a single-molecule desktop sequencer, GenoCare 1600 (GenoCare), which utilizes amplification-free library preparation and two-color sequencing-by-synthesis chemistry, making it more user-friendly compared with previous single-molecule sequencing platforms for clinical use. Using the GenoCare platform, we sequenced an Escherichia coli standard sample and achieved a consensus accuracy exceeding 99.99%. We also evaluated the sequencing performance of this platform in microbial mixtures and coronavirus disease 2019 (COVID-19) samples from throat swabs. Our findings indicate that the GenoCare platform allows for microbial quantitation, sensitive identification of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, and accurate detection of virus mutations, as confirmed by Sanger sequencing, demonstrating its remarkable potential in clinical application.

A study of pharmacists-joint total parenteral nutrition in haematopoietic cell transplantation in accord with diagnosis related groups: A retrospective clinical research.

Background: Within Diagnosis Related Groups, based on service capability, efficiency, and quality safety assessment, clinical pharmacists contribute to promoting rational drug utilisation in healthcare institutions. However, a deficiency of pharmacist involvement has been observed in the total parenteral nutrition support to patients following haematopoietic cell transplantation (HCT) within DRGs. Methods: This study involved 146 patients who underwent HCT at the Department of Haematology, the Second Affiliated Hospital of Dalian Medical University, spanning from January 2020 to December 2022. Results: Patients were allocated equally, with 73 in the control group and 73 in the pharmacist-involved group: baseline characteristics showed no statistics significance, including age, body mass index, nutrition risk screening-2002 score, liver and kidney function, etc. Albumin levels, prealbumin levels were significantly improved after a 7-day TPN support (34.92 ± 4.24 vs 36.25 ± 3.65, P = 0.044; 251.30 ± 95.72 vs 284.73 ± 83.15, P = 0.026). The body weight was increased after a 7-day support and before discharge (58.77 ± 12.47 vs 63.82 ± 11.70, P = 0.013; 57.61 ± 11.85 vs 64.92 ± 11.71, P < 0.001). The length of hospital stay, costs and the rate of re-admissions were significantly shortened (51.10 ± 1.42 vs 46.41 ± 1.86, P = 0.048; 360,162.67 ± 91,831.34 vs 324,070.16 ± 112,315.51, P = 0.035; 61.64% vs 43.84%, P = 0.046). Conclusions: Pharmacist-joint TPN support enhances the service efficiency score of medical units, ensuring the fulfilment of orders and rational medication.

The clinical effectiveness of sivelestat in treating sepsis patients with both acute respiratory distress syndrome and septic cardiomyopathy.

BACKGROUND: We aimed to assess the efficacy of the neutrophil elastase inhibitor, sivelestat, in the treatment of sepsis-induced acute respiratory distress syndrome (ARDS) and septic cardiomyopathy (SCM). METHODS: Between January 2019 and December 2021, we conducted a randomized trial on patients who had been diagnosed with sepsis-induced acute respiratory distress syndrome (ARDS) and septic cardiomyopathy (SCM) at Wuhan Union Hospital. The patients were divided into two groups by random envelop method, the Sivelestat group and the Control group. We measured the serum concentrations of Interleukin (IL)-6, IL-8, Tumor necrosis factor-α (TNF-α), and High-mobility group box 1 (HMGB1) at five time points, which were the baseline, 12 h, 24 h, 48 h, and 72 h after admission to the ICU. We evaluated the cardiac function by sonography and the heart rate variability (HRV) with 24-hour Holter recording between the time of admission to the intensive care unit (ICU) and 72 h after Sivelestat treatment. RESULTS: From January 2019 to December 2021, a total of 70 patients were included in this study. The levels of IL-6, IL-8, and TNF-α were significantly lower in the Sivelestat group at different time points (12 h, 24 h, 48 h, and 72 h). HMGB1 levels were significantly lower at 72 h after Sivelestat treatment (19.46 ± 2.63pg/mL vs. 21.20 ± 2.03pg/mL, P = 0.003). The stroke volume (SV), tricuspid annular plane systolic excursion (TAPSE), early to late diastolic transmitral flow velocity (E/A), early (e') and late (a') diastoles were significantly low in the Control group compared with the Sivelestat group. Tei index was high in the Control group compared with the Sivelestat group (0.60 ± 0.08 vs. 0.56 ± 0.07, P = 0.029). The result of HRV showed significant differences in standard deviation of normal-to-normal intervals (SDNN), low frequency (LF), and LF/HF (high frequency) between the two groups. CONCLUSIONS: Sivelestat can significantly reduce the levels of serum inflammatory factors, improve cardiac function, and reduce heart rate variability in patients with Sepsis-induced ARDS and SCM.

Prognostic value of plasma Aß1-40 for Alzheimer's disease.

OBJECTIVE: To investigate the clinical significance of plasma p-amyloid 1-40 (Aß1-40) in patients with Alzheimer's disease (AD). METHODS: In this retrospective study, the clinical data of 305 patients, with or without Alzheimer's disease (AD), who were treated at the Affiliated Hospital of Youjiang Medical University for Nationalities and the People's Hospital of Baise between January 2018 and December 2021 were analyzed. Patients were divided into two groups: an AD group (n=147) and a non-AD group (without AD, n=158 cases). Blood test indices, including serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine (CRE), high-sensitivity C-reactive protein (hsCRP), and plasma ß-amyloid 1-40 were collected and compared between the two groups. RESULTS: The plasma ß-amyloid 1-40 in the AD group was (3.71±3.45) mol/L, which was significantly higher than (2.8±1.35) mmol/L in the non-AD group (P<0.05). Similarly, hsCRP expression was significantly higher in the AD group than that in the non-AD group (P<0.05). There were no significant differences in AST, ALT, UA, T-tau, NFL or Cr levels between the two groups (all P>0.05). Moreover, univariate regression analysis showed that plasma ß-amyloid 1-40 and hsCRP were significantly correlated with AD. Multiple regression analysis demonstrated that plasma p-amyloid 1-40 (P<0.0001) and hsCRP (P=0.002) were independent predictors of AD. CONCLUSION: Plasma p-amyloid 1-40 and hsCRP are closely related to AD, and may serve as important clinical predictors of AD.

Acute encephalitis induced Kleine-Levin syndrome with episodic vertical gaze dysfunction during hypersomnia episodes.

Kleine-Levin syndrome (KLS) is a rare, recurring sleep disorder that easily ignored. Episodic upward-gaze palsy is an uncommon manifestation observed in patients of KLS, which further complicates this disorder. Although peripheral microbial infection have been recognized as most common triggers for KLS, the underlying pathophysiology of this disorder remains unclear. We reported an unique case of KLS elicited by acute encephalitis, which was confirmed by pleocytosis of cerebrospinal fluid (CSF) at the early stage. The CSF returned to normal over time while the attacks continued to recur frequently. Episodic upward-gaze palsy was observed during attacks and clinical symptoms were exacerbated following a subsequent COVID-19 infection. This report presents a classic KLS case with distinctive characteristics, which should facilitate more accurate and earlier diagnosis for clinicians. Furthermore, it provides a new perspective for understanding the pathogenesis of this rare disease.

Delayed postoperative neurological deficits from scoliosis correction: a case series and systematic review on clinical characteristics, treatment, prognosis, and recovery.

OBJECTIVE: This study was designed to investigate the clinical features, treatment modalities, and risk factors influencing neurological recovery in patients who underwent scoliosis correction with delayed postoperative neurological deficit (DPND). METHODS: Three patients with DPND were identified from 2 central databases for descriptive analysis. Furthermore, all DPND cases were retrieved from the PubMed and Embase databases. Neurological function recovery was categorized into complete and incomplete recovery groups based on the American Spinal Injury Association (ASIA) impairment scale. RESULTS: Two patients were classified as type 3, and one was classified as type 2 based on the MRI spinal cord classification. Intraoperative neurophysiological monitoring (IONM) was consistently negative throughout the corrective procedure, and intraoperative wake-up tests were normal. The average time to DPND development was 11.8 h (range, 4-18 h), and all three patients achieved complete recovery of neurological function after undergoing revision surgery. A total of 14 articles involving 31 patients were included in the literature review. The mean time to onset of DPND was found to be 25.2 h, and 85.3% (29/34) of patients experienced DPND within the first 48 h postoperatively, with the most common initial symptoms being decreased muscle strength and sensation (26 patients, 83.9%). Regarding neurological function recovery, 14 patients were able to reach ASIA grade E, while 14 patients were not able to reach ASIA grade E. Univariate analysis revealed that preoperative diagnosis (p = 0.004), operative duration (p = 0.017), intraoperative osteotomy method (p = 0.033), level of neurological deficit (p = 0.037) and deficit source (p = 0.0358) were significantly associated with neurological outcomes. Furthermore, multivariate regression analysis indicated a strong correlation between preoperative diagnosis (p = 0.003, OR, 68.633; 95% CI 4.299-1095.657) and neurological prognosis. CONCLUSION: Our findings indicate that spinal cord ischemic injury was a significant factor for patients experiencing DPND and distraction after corrective surgery may be a predisposing factor for spinal cord ischemia. Additionally, it is important to consider the possibility of DPND when limb numbness and decreased muscle strength occur within 48 h after corrective scoliosis surgery. Moreover, emergency surgical intervention is highly recommended for DPND caused by mechanical compression factors with a promising prognosis for neurological function, emphasizing the importance of taking into account preoperative orthopedic diagnoses when evaluating the potential for neurological recovery.

Room-Temperature Phase Transition Material with Switchable Second-Order Nonlinear Optical Properties.

Phase transition materials with switchable second-order nonlinear optical (NLO) properties have attracted extensive attention because of their great application potential in photoelectric switches, sensors, and modulators, while metal-free organics with NLO switchability near room temperature remain scarce. Herein, we report a hydrogen-bonded metal-free organic crystal, 2-methylpropan-2-aminium 2,2-dimethylpropanoate (1), exhibiting a room-temperature phase transition and favorable NLO switchability. Through investigations on its thermal anomalies, dielectric properties, and crystal structures, we uncover that 1 holds a near-room-temperature phase transition at 303 K from noncentrosymmetric point group C2v to centrosymmetric one D2h, which is attributed to the order-disorder transformations of both tert-butylamine cations and dimethylpropionic acid anions. Accompanied by symmetry change during the phase transition, 1 exhibits reversible and repeatable NLO "on-off" switchability with a desirable switching contrast ratio of ca. 19 between high and low NLO states. This discovery demonstrates a metal-free organic crystal with NLO switching behavior near room temperature, serving as a promising candidate in smart and ecofriendly photoelectric functional materials and devices.

AP-1 and SP1 trans-activate the expression of hepatic CYP1A1 and CYP2A6 in the bioactivation of AFB1 in chicken.

Dietary exposure to aflatoxin B1 (AFB1) is harmful to the health and performance of domestic animals. The hepatic cytochrome P450s (CYPs), CYP1A1 and CYP2A6, are the primary enzymes responsible for the bioactivation of AFB1 to the highly toxic exo-AFB1-8,9-epoxide (AFBO) in chicks. However, the transcriptional regulation mechanism of these CYP genes in the liver of chicks in AFB1 metabolism remains unknown. Dual-luciferase reporter assay, bioinformatics and site-directed mutation results indicated that specificity protein 1 (SP1) and activator protein-1 (AP-1) motifs were located in the core region -1,063/-948, -606/-541 of the CYP1A1 promoter as well as -636/-595, -503/-462, -147/-1 of the CYP2A6 promoter. Furthermore, overexpression and decoy oligodeoxynucleotide technologies demonstrated that SP1 and AP-1 were pivotal transcriptional activators regulating the promoter activity of CYP1A1 and CYP2A6. Moreover, bioactivation of AFB1 to AFBO could be increased by upregulation of CYP1A1 and CYP2A6 expression, which was trans-activated owing to the upregulalion of AP-1, rather than SP1, stimulated by AFB1-induced reactive oxygen species. Additionally, nano-selenium could reduce ROS, downregulate AP-1 expression and then decrease the expression of CYP1A1 and CYP2A6, thus alleviating the toxicity of AFB1. In conclusion, AP-1 and SP1 played important roles in the transactivation of CYP1A1 and CYP2A6 expression and further bioactivated AFB1 to AFBO in chicken liver, which could provide novel targets for the remediation of aflatoxicosis in chicks.

Two-dimensional tetragonal AlOX (X = Cl, Br, or I) monolayers with promising photocatalytic performance: first-principles investigations.

It is of great significance to search for new two-dimensional materials with excellent photocatalytic water splitting properties. Here, the AlOX (X = Cl, Br, or I) monolayers were constructed to explore their electronic and optical properties as a potential photocatalyst and mechanism of high photocatalytic activity by first principles calculations, for the first time. The results show that the AlOX (X = Cl, Br, or I) monolayers are all dynamically and thermodynamically stable. It is found that the AlOI monolayer exhibits visible optical absorption with a 538 nm absorption band edge, due to its direct band gap of 2.22 eV. Moreover, an appropriate band edge potential ensures its excellent reduction-oxidation (redox) ability. The asymmetry of crystals along different directions results in a noncoplanar HOMO and LUMO as well as an anisotropy effective mass and favors the separation of photogenerated carriers. These findings present the potential of the AlOX (X = Cl, Br, or I) monolayers as photocatalysts.

Metabolomics and transcriptomics reveal the mechanism of alkaloid synthesis in Corydalis yanhusuo bulbs.

Corydalis yanhusuo W.T. Wang is a traditional herb. Benzylisoquinoline alkaloids (BIAs) are the main pharmacological active ingredients that play an important role in sedation, relieving pain, promoting blood circulation, and inhibiting cancer cells. However, there are few studies on the biosynthetic pathway of benzylisoquinoline alkaloids in Corydalis yanhusuo, especially on some specific components, such as tetrahydropalmatine. We carried out widely targeted metabolome and transcriptomic analyses to construct the biosynthetic pathway of benzylisoquinoline alkaloids and identified candidate genes. In this study, 702 metabolites were detected, including 216 alkaloids. Protoberberine-type and aporphine-type alkaloids are the main chemical components in C. yanhusuo bulbs. Key genes for benzylisoquinoline alkaloids biosynthesis, including 6-OMT, CNMT, NMCH, BBE, SOMT1, CFS, SPS, STOX, MSH, TNMT and P6H, were successfully identified. There was no significant difference in the content of benzylisoquinoline alkaloids and the expression level of genes between the two suborgans (mother-bulb and son-bulb). The expression levels of BIA genes in the expansion stage (MB-A and SB-A) were significantly higher than those in the maturity stage (MB-C and SB-C), and the content of benzylisoquinoline alkaloids was consistent with the pattern of gene regulation. Five complete single genes were likely to encode the functional enzyme of CoOMT, which participated in tetrahydropalmatine biosynthesis in C. yanhusuo bulbs. These studies provide a strong theoretical basis for the subsequent development of metabolic engineering of benzylisoquinoline alkaloids (especially tetrahydropalmatine) of C. yanhusuo.