Green and efficient catalytic oxidation of ethylbenzene to acetophenone over cobalt oxide supported on a carbon material derived from sugar.

The use of biomass as a carbon source to support metal oxides has significant advantages in environmental protection and reducing the cost of the catalyst. The critical point lies on the development of highly active and recyclable catalysts. In this study, sugar was used as a carbon source, and cobalt oxide was loaded via an in situ method and an impregnation method to prepare the catalyst, respectively. The catalysts were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), X-ray powder diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FT-IR) spectroscopy, Raman, in situ electron paramagnetic resonance (in situ EPR) and N2 adsorption-desorption. The characterization results show that the macroporous carbon-supported cobalt oxide catalyst prepared by the in situ method contains CoOx nanoparticles on the support, but the dispersion of cobalt oxide on the support is more uniform compared with the catalyst prepared by the impregnation method. The catalytic performance of the prepared catalyst was evaluated through the oxidation of ethylbenzene (EB) to acetophenone (AP) as a probe reaction. Under the optimized reaction conditions, temperature (T) = 80 °C, m(catalyst) : m(EB) = 0.15, n(H2O2) : n(EB) : n(KBr) = 14.4 : 1 : 0.1, t = 8 h, and V(EB) : V(CH3COOH) = 1 : 10, the conversion of EB and the selectivity of AP were 84.1% and 81.3%, respectively. CoOx/SC-10-in situ exhibits improved reactivity of EB oxidation owing to cobalt ions on the carbon support that promote the free radical and acid catalytic reaction pathway. The cobalt oxide catalyst supported by biomass carbon has decent recycling and regeneration ability, which provides a new idea for the application of biomass.

Causal effect of COVID-19 on longitudinal volumetric changes in subcortical structures: A mendelian randomization study.

A few observational neuroimaging investigations have reported subcortical structural changes in the individuals who recovered from the coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the causal relationships between COVID-19 and longitudinal changes of subcortical structures remain unclear. We performed two-sample Mendelian randomization (MR) analyses to estimate putative causal relationships between three COVID-19 phenotypes (susceptibility, hospitalization, and severity) and longitudinal volumetric changes of seven subcortical structures derived from MRI. Our findings demonstrated that genetic liability to SARS-CoV-2 infection had a great long-term impact on the volumetric reduction of subcortical structures, especially caudate. Our investigation may contribute in part to the understanding of the neural mechanisms underlying COVID-19-related neurological and neuropsychiatric sequelae.

Off-Stoichiometry Thiol-Ene (OSTE) Micro Mushroom Forest: A Superhydrophobic Substrate.

Superhydrophobic surfaces have been used in various fields of engineering due to their resistance to corrosion and fouling and their ability to control fluid movement. Traditionally, superhydrophobic surfaces are fabricated via chemical methods of changing the surface energy or mechanical methods of controlling the surface topology. Many of the conventional mechanical methods use a top-to-bottom scheme to control the surface topolopy. Here, we develop a novel fabrication method of superhydrophobic substrates using a bottom-to-top scheme via polymer OSTE, which is a prototyping polymer material developed for the fabrication of microchips due to its superior photocuring ability, mechanical properties, and surface modification ability. We fabricate a superhydrophobic substrate by OSTE-OSTE micro mushroom forest via a two-step lithography process. At first, we fabricate an OSTE pillar forest as the mushroom stems; then, we fabricate the mushroom heads via backside lithography with diffused UV light. Such topology and surface properties of OSTE render these structures superhydrophobic, with water droplets reaching a contact angle of 152.9 ± 0.2°, a sliding angle of 4.1°, and a contact angle hysteresis of less than 0.5°. These characteristics indicate the promising potential of this substrate for superhydrophobic applications.

Estimating the effect of inclisiran on hypercholesterolemia and primary prevention of cardiovascular disease: the NHANES 1999-2018 study.

BACKGROUND: Hypercholesterolemia has been identified as an independent predictor of cardiovascular disease (CVD). Inclisiran, an innovative small interfering RNA agent, is anticipated to result in a notable reduction of approximately 50% in low-density lipoprotein cholesterol (LDL-C) levels. Given its transformative impact, this study scrutinized the eligibility of the US population for inclisiran treatment and evaluated its potential effects on hypercholesterolemia and the primary prevention of CVD. METHODS: This study applied the eligibility criteria from the ORION 10 and 11 trials to the 1999-2018 National Health and Nutrition Examination Survey (NHANES) dataset to estimate the size of the eligible population for atherosclerotic cardiovascular disease (ASCVD) and ASCVD-risk equivalents. Utilizing the reduction in LDL-C levels from ORION 10, this study predicted the impact of inclisiran on LDL-C levels among ASCVD patients. Similarly, leveraging the changes in lipid levels from ORION 11, this study predicted inclisiran's effect on the 10-year change in CVD risk and preventable CVD events in the ASCVD-risk equivalents population, employing the Framingham CVD Risk Score. RESULTS: The study identified 579 ASCVD patients (5 million) and 382 ASCVD-risk equivalents (2.66 million) who met the eligibility criteria from ORION 10 and 11. Among the ASCVD population, 3.5 million (70.2%) would achieve a ≥ 50% reduction in LDL-C levels after treatment. Furthermore, 4.6 million (91.3%) would achieve LDL-C levels < 70 mg/dL, and 3.8 million (75%) would achieve LDL-C levels < 55 mg/dL after treatment. For the ASCVD-risk equivalents population, the estimated 10-year CVD risk would decrease from 25.3 to 17.7%, an absolute reduction of 7.6% and a relative reduction of 30% following inclisiran treatment, potentially preventing 202,353 CVD events over a decade, including 138,084 coronary heart disease cases, 37,351 strokes, and 23,894 congestive heart failure cases. CONCLUSIONS: Inclisiran has the potential to substantially reduce the prevalence of hypercholesterolemia and prevent nearly 200,000 CVD events in eligible US adults.

One-Stage Surgical Management for Cervical Pyogenic Spondylodiscitis by Anterior Debridement, Reconstruction, and Instrumentation: A Single-Center Experience.

OBJECTIVE: Surgical treatment is an effective strategy for cervical pyogenic spondylodiscitis (CPS). However, the optimal surgical approach is uncertain. This study was conducted to evaluate the clinical efficacy of debridement, reconstruction, and instrumentation via the anterior-only approach for CPS. METHODS: We retrospectively collected the data of patients with CPS who underwent one-stage anterior debridement, reconstruction, and instrumentation from January 2013 to December 2022. The surgical duration and blood loss volume were analyzed. The Frankel grading classification was used to evaluate the improvement in neurological function. The visual analog scale and Japanese Orthopaedic Association scores were used to evaluate neck pain and functional recovery. The radiological parameters of regional lordosis angle and C2-C7 Cobb angle were used to evaluate the recovery of cervical alignment. C-reactive protein and erythrocyte sedimentation rate were evaluated to assess the control of infection. RESULTS: Totally, 32 patients were eligible. The surgical duration was 118.9 ± 14.3 minutes, and the blood loss volume was 88.4 ± 42.7 mL. Significant improvements in the Frankel grading were observed in patients with neurological deficits. The visual analog scale and Japanese Orthopaedic Association scores significantly improved postoperatively and during follow-up (P < 0.01). The regional lordosis angle significantly increased from 4.0° ± 6.6° preoperatively to 8.4° ± 5.8° at the final follow-up (P < 0.01). The C2-C7 Cobb angle increased from 11.1° ± 7.1° preoperatively to 13.8° ± 7.2° at the final follow-up (P < 0.01). Bony fusion occurred in all patients. C-reactive protein and erythrocyte sedimentation rate significantly decreased postoperatively and returned to normal during follow-up. CONCLUSIONS: One-stage debridement, reconstruction, and instrumentation via the anterior approach is an effective surgical strategy for CPS. In addition to surgery, targeted and prolonged antibiotic therapy is of crucial importance.

Automatic characterization of capillary flow profile of liquid samples on µTADs based on capacitance measurement.

Capillary flow profile of liquid samples in porous media is closely related to the important properties of liquid samples, including the viscosity and the surface energy. Therefore, capillary flow profile can be used as an index to differentiate liquid samples with different properties. Fast and automatic characterization of capillary flow profile of liquid samples is necessary. In this work, we develop a portable and economical capacitance acquisition system (CASY) to easily obtain the capillary flow profile of liquid samples on microfluidic thread-based analytical devices (µTADs) by measuring the capacitance during the capillary flow. At first, we validate the accuracy of this method by comparing with the traditional method by video analysis in obtaining the capillary flow profiles in µTADs of cotton threads or glass fiber threads. Then we use it to differentiate liquid samples with different viscosity (mixture of water and glycerol). In addition, capillary flow profile on µTADs with chemical valves (chitosan or sucrose) can also be obtained on this device. Lastly, we show the potential of this device in measurement of hematocrit (HCT) of whole blood samples. This device can be used to catalog liquid biological samples with different properties in point-of-care diagnostics in the near future.

Discovery of SIRT1-Activating Hydrogen Sulfide Donating Derivatives for Efficient Resistant of Myocardial Ischemic Injury.

Activating SIRT1 or promoting SIRT1 expression are both protective against myocardial ischemia. Combining these approaches would be an effective strategy for treating ischemic heart disease. Herein, we identified lead compounds with SIRT1 activation activity through screening the natural product library, and five series of H2S donating derivatives were designed and synthesized. Among them, compound 17 exerted an effective cardioprotective effect in vitro and in vivo. The addition of H2S scavenger attenuated the protective activity, emphasizing the critical involvement of H2S in the myocardial ischemia process. Interestingly, 17 exhibited stronger direct SIRT1 activative ability and induced higher SIRT1 expression capability compared to the lead. Furthermore, 17 attenuates oxidative stress-induced cardiomyocytes apoptosis by activating the SIRT1-PGC1α signaling pathway. Our study validated the promising potential of activating SIRT1 and promoting SIRT1 expression through H2S to improve cardiomyocytes function, providing novel insights into the protective mechanisms during the progression of ischemic heart disease.

Effects of tauroursodeoxycholate on arsenic-induced hepatic injury in mice: A comparative transcriptomic analysis.

BACKGROUND: Prolonged exposure to excessive arsenic (As) and its compounds can cause damage to multiple systems, including respiratory, cardiovascular, immune, nervous, and endocrine systems. Manifestations include changes in skin pigmentation, excessive keratosis on palms and soles, gastrointestinal symptoms, and anemia. The liver as an important detoxification organ of the body, is a significant target organ for arsenic toxicity, and liver diseases are common. So far, the molecular mechanism has not been fully elucidated. Evidence suggests that taurodeoxycholic acid (TUDCA) has a protective role in arsenic-induced liver injury. This study aims to reveal potential target genes at the transcriptional level following TUDCA intervention, providing insights for the intervention of arsenic-induced liver injury. METHODS: The TUDCA intervention model of arsenic liver injury in C57BL/6 N mice was established. The experiment was divided into two phases and lasted for 24 weeks. The phase I trial (12 weeks) was divided into control, low, middle and high groups according to the dose of As. The phaseⅡtrial (12 weeks) was administered in combination with 10 mg/L sodium arsenite (the first stage high arsenic group) and TUDCA, so subsequent groups was named with H indicating high arsenic. Divide into four groups: control group(C), TUDCA solvent control group(H-Vehicle), TUDCA combined with As group(H-TUDCA), arsenic group (As). As was ingested through free water and TUDCA was administered to mice by gavage at a dose of 0.1 mL/10 g.b.w (100 mg/kg) once a day for 12 weeks. The differential expression gene (DEG) profile was obtained from the second batch of mouse liver tissues by RNA sequencing technology. Comparative transcriptomic analysis methods were used to identify co-varying DEGs between arsenic induction and TUDCA intervention, along with their associated pathways. QRT-PCR was utilized for validation. RESULTS: Transcriptome results showed that 487 DEGs were identified after arsenic induction. TUDCA intervention identified 231 DEGs (p-values < 0.05 and | log2(fold change) | > 1). The comparison of "AS vs C" and "H_TUDCA vs AS" identified 65 covariant DEGs, and further screened the TUDCA pathways and related genes among these genes，six pathways and 11 genes (Ccl21a, Ccr7, Mdm2, Slc2a4, Akr1b7, Pnpla3, Dusp8, Hspa1a, Cyp7a1, Cybrd1, Trpm6) were obtained. Next, we screened for covariant DEGs among the top 50 potential hub genes in arsenic-induced DEGS, and obtained 7 (Hbb-bs, Hspa1a, Mdm2, Slc2a4, Ptk6, Egr1, and Dusp8). Finally, the intersection of Hub gene and pathway gene was selected as the target genes Dusp8, Hspa1a, Mdm2 and Slc2a4. The sequencing results showed that the mRNA expressions of Dusp8, Hspa1a and Mdm2 were significantly increased after arsenic induction, while the expression of Slc2a4 was significantly decreased (P<0.05). Conversely, TUDCA intervention reversed these DEGs changes, consistent with QRT-PCR validation results. CONCLUSION: This study contributes to understanding the potential health effects of arsenic-induced liver injury, identifying new potential targets, and providing references for TUDCA intervention.

A preliminary study of T-2 toxin that cause liver injury in rats via the NF-kB and NLRP3-mediated pyroptosis pathway.

T-2 toxin is recognized as the most potent and prevalent secondary metabolite among monotrichous mycotoxins produced by Fusarium species. Multiple studies have substantiated the hepatotoxic effects of T-2 toxin. This study aimed to investigate whether NF-κB and NLRP3-mediated pyroptosis is involved in the underlying mechanism of T-2 toxin hepatotoxicity. We designed three groups of rat models, blank control; solvent control and T-2 toxin (0.2 mg/kg body weight/day), which were euthanized at week 8 after gavage staining of the toxin. Through HE staining and biochemical indicators associated with liver injury, we observed that T-2 toxin induced liver damage in rats. By Western blot analysis and qRT-PCR, we found that the expression levels of pyroptosis-related genes and proteins were significantly higher in the T-2 toxin group. In addition, we also found a significant increase in the expression of p-NF-κB protein, an upstream regulator of NLRP3. In conclusion, NF-κB and NLRP3-mediated pyroptosis may be involved in the mechanism of hepatotoxic action of T-2 toxin, which provides a new perspective.

Circ_0006174 Upregulates IGF1R to Enhance Radioresistance and Tumorigenesis in Colorectal Cancer via miR-940 Suppression.

Colorectal cancer (CRC) is one of the most common malignancies all over the world. Increasing evidence has revealed that circular RNAs (circRNAs) are involved in the progression of CRC. In this study, we aimed to investigate the role and underlying mechanism of circ_0006174 in the development and radiosensitivity of CRC. Circ_0006174, microRNA-940 (miR-940), and insulin-like growth factor 1 receptor (IGF1R) expression levels were evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). The radiosensitivity of cells also was assessed using colony formation assay. Besides, cell proliferation, apoptosis, migration, and invasion were detected by cell counting kit-8 (CCK-8), flow cytometry, and transwell assays. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to verify the relationship between miR-940 and circ_0006174 or IGF1R. IGF1R protein level was examined using western blot. A xenograft tumor model was used to verify the function of circ_0006174 in CRC tumor growth in vivo. Circ_0006174 and IGF1R levels were elevated and miR-940 expression was decreased in CRC tissues and cells. Circ_0006174 knockdown enhanced the radiosensitivity of CRC cells by regulating cell proliferation, apoptosis, migration, and invasion in vitro. In mechanism, circ_0006174 served as a sponge for miR-940 to upregulate IGF1R expression. Moreover, circ_0006174 silencing suppressed CRC growth in vivo. Circ_0006174 boosts radioresistance of CRC cells at least partly through upregulating IGF1R expression by sponging miR-940, providing a novel theoretical basis for CRC therapy.

Recent advances of metal active sites in photocatalytic CO2 reduction.

Photocatalytic CO2 reduction captures solar energy to convert CO2 into hydrocarbon fuels, thus shifting the dependence on rapidly depleting fossil fuels. Among the various proposed photocatalysts, systems containing metal active sites (MASs) possess obvious advantages, such as effective photogenerated carrier separation, suitable adsorption and activation of intermediates, and achievable C-C coupling to generate multi-carbon (C2+) products. The present review aims to summarize the typical photocatalytic materials with MAS, highlighting the critical role of different formulations of MAS in CO2 photoreduction, especially for C2+ product generation. State-of-the-art progress in the characterization and theoretical calculations for MAS-containing photocatalysts is also emphasized. Finally, the challenges and prospects of catalytic systems involving MAS for solar-driven CO2 conversion are outlined, providing inspiration for the future design of materials for efficient photocatalytic energy conversion.

Photothermal-Driven Droplet Manipulation: A Perspective.

Optofluidics, which utilizes the interactions between light and fluids to realize various functions, has garnered increasing attention owing to the advantages of operational simplicity, exceptional flexibility, rapid response, etc. As one of the typical light-fluid interactions, the localized photothermal effect serving as a stimulus has been widely used for fluid manipulation. Particularly, significant progress on photothermal-driven droplet manipulation has been made. In this perspective, recent advancements in localized photothermal effect driven droplet manipulation are summarized. First, the photothermal manipulation of droplets on open surfaces is outlined. An attractive droplet manipulation of light droplet levitation above the gas-liquid interface via localized photothermal effect is then discussed. Besides, the photothermal-driven manipulation of droplets in an immiscible liquid phase is also discussed. Although promising, further development of photothermal-driven droplet manipulation is still needed. The challenges and perspectives of this light droplet manipulation strategy for broad implementation are summarized, which will help future studies and applications.

Biomarker-driven molecular imaging probes in radiotherapy.

Background: Biomarker-driven molecular imaging has emerged as an integral part of cancer precision radiotherapy. The use of molecular imaging probes, including nanoprobes, have been explored in radiotherapy imaging to precisely and noninvasively monitor spatiotemporal distribution of biomarkers, potentially revealing tumor-killing mechanisms and therapy-induced adverse effects during radiation treatment. Methods: We summarized literature reports from preclinical studies and clinical trials, which cover two main parts: 1) Clinically-investigated and emerging imaging biomarkers associated with radiotherapy, and 2) instrumental roles, functions, and activatable mechanisms of molecular imaging probes in the radiotherapy workflow. In addition, reflection and future perspectives are proposed. Results: Numerous imaging biomarkers have been continuously explored in decades, while few of them have been successfully validated for their correlation with radiotherapeutic outcomes and/or radiation-induced toxicities. Meanwhile, activatable molecular imaging probes towards the emerging biomarkers have exhibited to be promising in animal or small-scale human studies for precision radiotherapy. Conclusion: Biomarker-driven molecular imaging probes are essential for precision radiotherapy. Despite very inspiring preliminary results, validation of imaging biomarkers and rational design strategies of probes await robust and extensive investigations. Especially, the correlation between imaging biomarkers and radiotherapeutic outcomes/toxicities should be established through multi-center collaboration involving a large cohort of patients.

The roles and potential mechanisms of plant polysaccharides in liver diseases: a review.

Plant polysaccharides (PP) demonstrate a diverse array of biological and pharmacological properties. This comprehensive review aims to compile and present the multifaceted roles and underlying mechanisms of plant polysaccharides in various liver diseases. These diseases include non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), fibrosis, drug-induced liver injury (DILI), and hepatocellular carcinoma (HCC). This study aims to elucidate the intricate mechanisms and therapeutic potential of plant polysaccharides, shedding light on their significance and potential applications in the management and potential prevention of these liver conditions. An exhaustive literature search was conducted for this study, utilizing prominent databases such as PubMed, Web of Science, and CNKI. The search criteria focused on the formula "(plant polysaccharides liver disease) NOT (review)" was employed to ensure the inclusion of original research articles up to the year 2023. Relevant literature was extracted and analyzed from these databases. Plant polysaccharides exhibit promising pharmacological properties, particularly in the regulation of glucose and lipid metabolism and their anti-inflammatory and immunomodulatory effects. The ongoing progress of studies on the molecular mechanisms associated with polysaccharides will offer novel therapeutic strategies for the treatment of chronic liver diseases (CLDs).

Design and synthesis of 6,20-epoxy A-ring modified oridonin derivatives with antitumor activity through extrinsic and mitochondrial pathways.

Oridonin is an antitumor ent-kaurane diterpenoid that medicinal chemists have been paying close attention to in recent years. Herein, a novel 6,20-epoxy A-ring modified oridonin derivative 2 was obtained by a 6-step synthesis. A series of 14-O derivatives of 2 (EpskA1-EpskA24) were synthesized to further enhance the activity. Based on their cytotoxicity against MCF-7, A549 and L-02 cells, EpskA9, EpskA10 and EpskA21 were chosen for further screening to obtain a wider antitumor spectrum. Collectively, EpskA21 showed the most potent antiproliferative activity, inhibiting proliferation and migration, and inducing apoptosis and cell cycle arrest in MCF-7 and MIA-PaCa-2 cells. With the help of network pharmacology analysis, apoptosis-related proteins were selected and further tested by western blot assay. The inhibition of PI3K/AKT and an increase in the levels of Bax/Bcl-2 ratio, Cyt-C, cleaved-Caspase-9, cleaved-Caspase-3 and cleaved-PARP was observed, indicating that EpskA21 induced apoptosis through the mitochondrial pathway. Given that an increase in DR5 expression and activated Caspase-8 were also observed, the extrinsic apoptosis pathway might also be related to the antitumor effect.

An ultra-efficient pretreatment method adopted LPUV/CoFe2O4/PMS-based photolysis for accurate detection of Cd(II) and Pb(II) in water via SWASV.

Dissolved organic matter (DOM) is a widely occurring substance in rivers that can strongly complex with heavy metal ions (HMIs), severely interfering with the electrochemical signal of anodic stripping voltammetry (ASV) and reducing the detection accuracy of HMIs in water. In this study, we investigated a novel advanced oxidation process (AOP) that involves the activation of peroxymonosulfate (PMS) using low-pressure ultraviolet (LPUV) radiation and CoFe2O4 photocatalysis. This novel AOP was used for the first time as an effective pretreatment method to break or weaken the complexation between HMIs and DOM, thereby restoring the electrochemical signals of HMIs. The key parameters, including the PMS concentration, CoFe2O4 concentration, and photolysis time, were optimized to be 6 mg/L, 12 mg/L, and 30 s for eliminating DOM interference during the electrochemical analysis of HMIs via LPUV/CoFe2O4-based photolysis. Investigations of the microstructure, surface morphology, specific surface area, and pore volume of CoFe2O4 were conducted to reveal the exceptional signal recovery capability of LPUV/CoFe2O4/PMS-based photolysis in mitigating interference from DOM during HMIs analysis. The PMS activation mechanism, which is critical to the signal recovery process, was elucidated by analyzing the reactive oxygen species (ROS) and the surface elemental composition of CoFe2O4. Additionally, the degradation and transformation behavior of humus-HMIs complexes were analyzed to study the mechanism of ASV signal recovery further. Notably, the detection results of HMIs in actual water samples obtained using the proposed pretreatment method were compared with those obtained from ICP-MS, yielding an RMSE less than 0.04 µg/L, which indicated the satisfactory performance of the proposed pretreatment method for the ASV detection of HMIs in complex actual samples.

An Intelligent Hand-Assisted Diagnosis System Based on Information Fusion.

This research proposes an innovative, intelligent hand-assisted diagnostic system aiming to achieve a comprehensive assessment of hand function through information fusion technology. Based on the single-vision algorithm we designed, the system can perceive and analyze the morphology and motion posture of the patient's hands in real time. This visual perception can provide an objective data foundation and capture the continuous changes in the patient's hand movement, thereby providing more detailed information for the assessment and providing a scientific basis for subsequent treatment plans. By introducing medical knowledge graph technology, the system integrates and analyzes medical knowledge information and combines it with a voice question-answering system, allowing patients to communicate and obtain information effectively even with limited hand function. Voice question-answering, as a subjective and convenient interaction method, greatly improves the interactivity and communication efficiency between patients and the system. In conclusion, this system holds immense potential as a highly efficient and accurate hand-assisted assessment tool, delivering enhanced diagnostic services and rehabilitation support for patients.

Discovery of Novel Peptide Antagonists Targeting GPR55 for Liver Inflammation and Fibrosis.

Liver fibrosis is a condition characterized by aberrant proliferation of connective tissue in the liver resulting from diverse etiological factors. G protein-coupled receptor GPR55 has recently been identified as a regulator of liver diseases. Herein, we report the discovery of a cyclic peptide P1-1 that antagonizes GPR55 and suppresses collagen secretion in hepatic stellate cells. The alanine scanning and docking study was carried out to predict the binding mode and allowed for further structural optimization of peptide antagonists for GPR55. The subsequent in vivo study demonstrated that P1-1 ameliorates CCl4-induce and MCD-diet-induce acute liver inflammation and fibrosis. Further study indicates that P1-1 reduces reactive oxygen species (ROS) production, attenuates ER stress, and inhibits mitochondria-associated hepatocyte apoptosis. In this work, we provided the first successful example of antagonizing GPR55 for liver inflammation and fibrosis, which validates GPR55 as a promising target for the treatment of liver fibrosis and affords a high-potent GPR55 antagonist P1-1 as a potential therapeutic candidate.

Metabolomics and physio-chemical analyses of mulberry plants leaves response to manganese deficiency and toxicity reveal key metabolites and their pathways in manganese tolerance.

Introduction: Manganese (Mn) plays a pivotal role in plant growth and development. Aside aiding in plant growth and development, Mn as heavy metal (HM) can be toxic in soil when applied in excess. Morus alba is an economically significant plant, capable of adapting to a range of environmental conditions and possessing the potential for phytoremediation of contaminated soil by HMs. The mechanism by which M. alba tolerates Mn stresses remains obscure. Methods: In this study, Mn concentrations comprising sufficiency (0.15 mM), higher regimes (1.5 mM and 3 mM), and deficiency (0 mM and 0.03 mM), were applied to M. alba in pot treatment for 21 days to understand M. alba Mn tolerance. Mn stress effects on the net photosynthetic rate (Pn), stomatal conductance (Gs), transpiration rate (Tr), intercellular CO2 concentration (Ci), chlorophyll content, plant morphological traits, enzymatic and non-enzymatic parameters were analyzed as well as metabolome signatures via non-targeted LC-MS technique. Results: Mn deficiency and toxicity decrease plant biomass, Pn, Ci, Gs, Tr, and chlorophyll content. Mn stresses induced a decline in the activities of catalase (CAT) and superoxide dismutase (SOD), while peroxidase (POD) activity, and leaf Mn content, increased. Soluble sugars, soluble proteins, malondialdehyde (MDA) and proline exhibited an elevation in Mn deficiency and toxicity concentrations. Metabolomic analysis indicates that Mn concentrations induced 1031 differentially expressed metabolites (DEMs), particularly amino acids, lipids, carbohydrates, benzene and derivatives and secondary metabolites. The DEMs are significantly enriched in alpha-linolenic acid metabolism, biosynthesis of unsaturated fatty acids, galactose metabolism, pantothenate and CoA biosynthesis, pentose phosphate pathway, carbon metabolism, etc. Discussion and conclusion: The upregulation of Galactinol, Myo-inositol, Jasmonic acid, L-aspartic acid, Coproporphyrin I, Trigonelline, Pantothenol, and Pantothenate and their significance in the metabolic pathways makes them Mn stress tolerance metabolites in M. alba. Our findings reveal the fundamental understanding of DEMs in M. alba's response to Mn nutrition and the metabolic mechanisms involved, which may hold potential significance for the advancement of M. alba genetic improvement initiatives and phytoremediation programs.

Polygenic Score for Conscientiousness Is a Protective Factor for Reversion from Mild Cognitive Impairment to Normal Cognition.

Spontaneous reversion from mild cognitive impairment (MCI) to normal cognition (NC) is little known. Based on the data of the Genetics of Personality Consortium and MCI participants from Alzheimer's Disease Neuroimaging Initiative, the authors investigate the effect of polygenic scores (PGS) for personality traits on the reversion of MCI to NC and its underlying neurobiology. PGS analysis reveals that PGS for conscientiousness (PGS-C) is a protective factor that supports the reversion from MCI to NC. Gene ontology enrichment analysis and tissue-specific enrichment analysis indicate that the protective effect of PGS-C may be attributed to affecting the glutamatergic synapses of subcortical structures, such as hippocampus, amygdala, nucleus accumbens, and caudate nucleus. The structural covariance network (SCN) analysis suggests that the left whole hippocampus and its subfields, and the left whole amygdala and its subnuclei show significantly stronger covariance with several high-cognition relevant brain regions in the MCI reverters compared to the stable MCI participants, which may help illustrate the underlying neural mechanism of the protective effect of PGS-C.