[Determination of five veterinary drug residues in milk by ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap mass spectrometry based on modified chitosan membrane purification].

Milk is an important consumer product with high nutritional value. The presence of veterinary drug residues in milk owing to the indiscriminate use of veterinary drugs may affect consumer health. In the mass spectrometric analysis of trace compounds, chromatographic co-eluting components easily interfere with the mass spectral signals obtained, affecting the accuracy of qualitative and quantitative analyses. Matrix purification is a promising method to reduce the matrix effect. Chitosan is a natural biopolymer with numerous active functional groups such as amino, acetyl, and hydroxyl groups; these groups can adsorb lipids through hydrophobic and electrostatic interactions. Chitosan also has the advantages of low production cost, stable chemical properties, and convenient modification. Novel chitosan-based materials are promising candidates for lipid purification. In this study, a chitosan membrane was modified with trimethoxyoctadecylsilane (C18-CSM). C18-CSM was prepared through one-step hydrolysis and used as a dispersive solid phase extraction (DSPE) adsorbent to purify the matrix during milk pretreatment. We combined C18-CSM with ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap mass spectrometry (UHPLC-Q/Exactive Orbitrap MS) to develop an effective method for the extraction and determination of ofloxacin, enrofloxacin, ciprofloxacin, diazepam, and metronidazole in milk. C18-CSM was characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, and water contact angle testing. The results indicated that the material has a rough surface and uniformly dense cross-section. The water contact angle of C18-CSM was 104°, indicating its good hydrophobicity. The pretreatment conditions (extraction solvent, dosage of NaCl, extraction frequency, and dosage of C18-CSM) that influenced the recoveries of the five veterinary drugs were investigated in detail. The optimal conditions were established as follows: 5% formic acid in acetonitrile, 1 g NaCl, extraction 1 time, 20 mg C18-CSM. Separation was performed on a Hypersil GOLD VANQUISH column (100 mm×2.1 mm, 1.9 µm). The mobile phase consisted of 0.1% formic acid aqueous solution and 0.1% formic acid in acetonitrile, and was flowed at a rate of 0.3 mL/min. The sample injection volume was 1 µL, and the column temperature was maintained at 25 ℃. Mass spectrometric analysis was performed in positive electrospray ionization mode. To verify the necessity of the purification material, the matrix effect was investigated using the matrix-matched standard curve method. The use of C18-CSM reduced the matrix effects of the five necessity drugs from the range of -22%-8.8% to the range of -13%-3.6%, indicating that C18-CSM is a highly efficient DSPE material. Under optimal conditions, the developed method showed good linearities within the range of 0.5-100 µg/L, with correlation coefficients (r2)≥0.9970. The limits of detection(LODs) and quantification (LOQs) were 0.2 µg/L and 0.5 µg/L, respectively. To assess the accuracy and precision of the method, we prepared milk samples with three spiked levels (low, medium, and high). The recoveries of the five veterinary drugs were ranged from 79.5% to 115%, and the intra-day and inter-day relative standard deviations were 7.0%-13% (n=6) and 1.3%-11% (n=3), respectively. This study provides a simple, accurate, and reliable method for the rapid and simultaneous determination of the five veterinary drug residues in milk.

A noncanonical E3 ubiquitin ligase RNF41-mediated MYO1C stability promotes prostate cancer metastasis by inducing actin remodeling.

Prostate cancer bone metastasis is a predominant cause of death for prostate cancer (PCa) patients. However, the underlying mechanisms are poorly understood. Here, we report that high levels of RNF41 are associated with metastatic human prostate cancer. RNF41 silencing inhibits prostate cancer cell growth, cell migration and invasion in vitro and in vivo. Mechanistically, we identify that RNF41 induces K27- and K63-linked noncanonical polyubiquitination of MYO1C to enhance its stability and induce actin remodeling, which promotes PCa bone metastasis. RNF41 was significantly upregulated in metastatic prostate cancer tissues and positively associated with MYO1C expression. Furthermore, we show in intraarterial injected-bone metastasis xenograft model that targeting MYO1C stability by inhibition of RNF41 markedly suppressed PCa bone metastasis. Collectively, our findings identify RNF41 is an important regulator of prostate cancer cell growth and metastasis and targeting RNF41/MYO1C could be a valuable strategy to ameliorate prostate cancer progression and metastasis.

Endogenous attention enhances contrast appearance regardless of stimulus contrast.

There has been enduring debate on how attention alters contrast appearance. Recent research indicates that exogenous attention enhances contrast appearance for low-contrast stimuli but attenuates it for high-contrast stimuli. Similarly, one study has demonstrated that endogenous attention heightens perceived contrast for low-contrast stimuli, yet none have explored its impact on high-contrast stimuli. In this study, we investigated how endogenous attention alters contrast appearance, with a specific focus on high-contrast stimuli. In Experiment 1, we utilized the rapid serial visual presentation (RSVP) paradigm to direct endogenous attention, revealing that contrast appearance was enhanced for both low- and high-contrast stimuli. To eliminate potential influences from the confined attention field in the RSVP paradigm, Experiment 2 adopted the letter identification paradigm, deploying attention across a broader visual field. Results consistently indicated that endogenous attention increased perceived contrast for high-contrast stimuli. Experiment 3 employed equiluminant chromatic letters as stimuli in the letter identification task to eliminate potential interference from contrast adaption, which might have occurred in Experiment 2. Remarkably, the boosting effect of endogenous attention persisted. Combining the results from these experiments, we propose that endogenous attention consistently enhances contrast appearance, irrespective of stimulus contrast levels. This stands in contrast to the effects of exogenous attention, suggesting that mechanisms through which endogenous attention alters contrast appearance may differ from those of exogenous attention.

Scalable Fabrication of Ionic-Conductive Covalent Organic Framework Fibers for Capturing of Sustainable Osmotic Energy.

High-performance covalent organic framework (COF) fibers are demanded for an efficient capturing of blue osmotic power because of their excellent durability, simple integration, and large scalability. However, the scalable production of COF fibers is still very challenging due to the poor solubility and fragile structure of COFs. Herein, for the first time, it is reported that COF dispersions can be continuously processed into macroscopic, meter-long, and pure COF fibers using a wet spinning approach. The two presented COF fibers can be directly used for capturing of osmotic energy, avoiding the production of composite materials that require other additives and face challenges such as phase separation and environmental issues induced by the additives. A COF fiber exhibits power densities of 70.2 and 185.3 W m-2 at 50-fold and 500-fold salt gradients, respectively. These values outperform those of most reported systems, which indicate the high potential of COF fibers for capturing of blue osmotic energy.

Roadway rock burst prediction based on catastrophe theory.

In order to quantitatively calculate the critical depth and critical load of mines affected by rock burst, and to achieve effective prevention and control of rock burst in coal mines, this paper proposes a mechanical model for predicting the occurrence of rock burst in coal mine roadways based on catastrophe theory. Additionally, a theoretical calculation formula for initiating rock burst is derived. The first step was to establish a mechanical analysis model, which directly correlated with the in-situ stress, physical and mechanical characteristics of the coal-rock mass, and engineering structural parameters. Following this, a mechanical instability criterion was derived for the key load-bearing circle within the surrounding rock of the roadway. In the final step, the critical depth and load for rock burst initiation were verified for 25 distinct coal mines in China that were prone to rock burst hazards. The research results demonstrate that the discrepancy between the theoretically calculated critical depth and the actual measured statistical values was less than 35%. In addition, the difference between the theoretically determined critical depth and the value calculated by Pan Yishan was less than 32%. Notably, the ratio of the theoretically calculated critical load to the uniaxial compressive strength of the coal-rock mass ranged from 0.38 to 1.93. This aligns with empirical data on rock burst occurrences, as set out in the engineering classification standards for rock masses. These research outcomes substantiated the practical utility of the proposed theory, thereby laying a robust theoretical groundwork for the quantitative control of rock burst.

Mining and analysis of ADE signals of two camptothecin topoisomerase 1 inhibitors / 中国药房

OBJECTIVE To mine and analyze the adverse drug events （ADE） signals of two camptothecin topoisomerase 1 inhibitors， i.e. irinotecan and topotecan， and to provide reference for clinical medication safety. METHODS Based on the U.S. Food and Drug Administration Adverse Event Reporting System （FAERS） database， ADE report data for the aforementioned two drugs were extracted from January 1， 2004 to March 31， 2023. After processing the data， signal mining was conducted by using the reporting odds ratio in conjunction with the Bayesian confidence propagation neural network， followed by analysis. RESULTS A total of 14 738 relevant ADE reports were screened， among which 11 483 were associated with irinotecan and 3 255 with topotecan. The ADE reports for irinotecan were predominantly male， whereas for topotecan， they were predominantly female； the age of patients using the two drugs mainly concentrated in 45-＜75 years old. A total of 847 signals were detected， involving 24 system organ classes （SOCs）. Among them， 565 signals of irinotecan were detected， involving 24 SOCs， primarily concentrating on gastrointestinal disorders， general disorders and administration site conditions， blood and lymphatic system disorders； the most frequently reported ADE was diarrhea， and the ADE with the strongest signal intensity was cholinergic syndrome. A total of 282 signals of topotecan were detected， involving 22 SOCs， primarily concentrating on general disorders and administration site conditions， investigations， blood and lymphatic system disorders， and gastrointestinal disorders； the most frequently reported ADEs were death and anemia， and the ADE with the strongest signal intensity was febrile bone marrow aplasia. ADE signals for irinotecan such as metastatic colorectal cancer， peripheral sensory neuropathy， steatohepatitis， and those for topotecan such as iris atrophy， retinal degeneration， vitreous hemorrhage， were not documented in their respective drug instruction. CONCLUSIONS ADEs of irinotecan and topotecan primarily involve the digestive and hematologic systems， warranting close clinical monitoring. Cholinergic syndrome caused by irinotecan should be concerned. In addition， patients receiving irinotecan should also be monitored for ADE such as metastatic colorectal cancer， peripheral sensory neuropathy， steatohepatitis， and proteinuria； for patients using topotecan， enhanced surveillance of ocular diseases is recommended to ensure medication safety.

The effect of growth hormone on invasion and migration of colon cancer cells / 重庆医学

Objective To explore the effects of growth hormone(GH)on the proliferation,cycle,inva-sion,and migration of colon cancer cells and its possible mechanism.Methods GH3 cells with growth hor-mone-type pituitary adenoma were cultured in vitro,and the secretion of growth hormone in the supernatant of GH3 cells was detected by ELISA.Colon cancer LoVo cells in logarithmic growth phase were randomly divid-ed into the control group and the experimental group.PBS was added to the control group,while high concen-trations of recombinant GH were added to the experimental group.The two groups of cells were cultured in vitro under the same conditions.CCK-8 method was used to detect the proliferation of the cells.Flow cytome-try was used to detect the cell cycle.Transwell assay was used to detect the effect of growth hormone on the invasion and migration of the cells.Western blot was used to detect the expressions levels of E-cadherin,N-cadherin,Vimentin,and Snail-1 proteins in the cells.Results The results of ELISA showed that GH3 cells could secrete a large amount of GH,and the concentration of GH in the supernatant was(1 208±9)ng/mL.GH promoted cell growth in a dose-dependent manner within a certain concentration range,and GH 200 ng/mL was the optimal intervention concentration for subsequent experiments.Compared with the control group,the cell cycle in the experimental group changed from G1 phase to S phase and G2 phase,the ratio of G1 phase cells decreased,and the ratio of S phase cells and G2 phase cells increased(P<0.05).Compared with the control group,the number of the cell invasion and migration increased in the experimental group(P<0.05),the expression levels of N-cadherin,Vimentin,and Snail-1 was up-regulated,while the expression level of E-cadherin was down-regulated(P<0.05).Conclusion High concentration of GH promotes the prolifera-tion,invasion and migration of colon cancer cells,and induces the transition of cell cycle from G1 to S and G2 phases.The mechanism may be related to the epithelial-mesenchymal transition(EMT)of colon cancer cells promoted by high concentration of GH.

Current status of research on the diagnosis and specific treatment of glycogen storage disease type Ⅱ / 中华实用儿科临床杂志

Glycogen storage disease type Ⅱ (GSDⅡ) is a rare autosomal recessive disorder.Infant onset of GSDⅡ usually accompanies progressive cardiac hypertrophy and muscle weakness, and eventually dies of cardiopulmonary failure.GSDⅡ is mainly screened and diagnosed by enzymatic and genetic tests.Enzyme replacement therapy (ERT) is the only currently approved treatment of GSDⅡ, which can effectively improve the function of the affected organs and the survival.Gene therapy and substrate reduction therapy for GSDⅡ are also undergoing basic or clinical research.This review summarizes the current research status of the diagnosis and treatment of GSDⅡ at home and abroad, focusing on the influencing factors for the efficacy of specific treatment (especially ERT), dosing regimen, and ways to improve the efficacy.

Intravoxel incoherent motion for quantitative evaluating chronic allograft dysfunction / 中国医学影像技术

Objective To observe the value of diffusion weighted imaging intravoxel incoherent motion(IVIM)for quantitative evaluating chronic allograft dysfunction(CAD).Methods Totally 104 CAD patients were prospectively enrolled and were assigned into CAD 1,2 and 3 groups(n=11,61,32)based on impairment severity of estimated renal function,and 36 healthy volunteers were enrolled as control group.The true diffusion coefficient(D value),microcirculation perfusion diffusion coefficient(D*value)and perfusion score(f value)of renal cortex and medulla IVIM parameters were compared among groups and within groups to assess the value of IVIM parameters for diagnosing CAD.Results The D value of transplanted renal cortex in all CAD groups were lower than that in control group(all P＜0.05),which decreased among CAD 1,2 and 3 groups(all P＜0.05).The D value of transplanted kidney medulla in CAD 2 and 3 groups were lower than that in control group(both P＜0.05).The D*values of transplanted renal cortex in all CAD groups were lower than that in control group,while of renal medulla in CAD 2 and 3 groups were lower than that in control group(both P＜0.05).The f values of cortex and medulla in CAD 2 and 3 groups were lower than those in control group(all P＜0.05),while of cortex in CAD 3 group was lower than that in CAD 1 and 2 groups(both P＜0.05).The area under the curve(AUC)of cortical IVIM combined model for diagnosing CAD was 0.96,better than the D*value and f value(AUC=0.74,0.83,P＜0.05)but not significantly different with that of the D value(AUC=0.94,P=0.32).AUC of medullary IVIM combined model for diagnosing CAD was 0.91,better than that of D,D*and f value(AUC=0.80,0.67 and 0.80,all P＜0.05).Conclusion IVIM parameters could be used to quantitatively evaluate CAD.

Research and evaluation on dynamic accumulation of dry matter and quality of Isatis indigotica in Longdong area / 中成药

AIM To explore the laws in accumulation of dry matter and medicinal ingredients of Isatis indigotica Fort.in Longdong area,and determine the best harvest time to obtain the high-quality and high-yield medicinal plant.METHODS The I.indigotica had its agronomic traits investigated regularly;the accumulation laws of its uridine,guanosine,(R,S)-geichan and adenosine measured by HPLC;and its comprehensive utilization value in different periods evaluated by grey correlation method.RESULTS There existed significant variations among the plant height,plant width,leaf length,leaf width,number of leaves,leaf weight,root length,root diameter,root weight,and the yields of uridine,guanosine,(R,S)-goitrin and adenosine at different growth stages,whose peak values appeared in different period.Additionally,there were also obvious differences in the aforementioned indexes levels among different strains.The highest weighted correlation degree of the comprehensive utilization value of Longde and 2008-6-2 on October 9,and of 2008-11 and 2016-2 on October 24.On the whole,the 2008-6-2 and 2016-2 were superior to 2008-11 and Longde.CONCLUSION It is suggested that the best harvest time of I.indigotica in Longdong area is in mid to late October.

Four cases of COVID-19 associated Guillain-Barré syndrome / 中华神经科杂志

COVID-19 associated Guillain-Barré syndrome (GBS) caused by peripheral nerve damage after SARS-CoV-2 infection is one of the most common COVID-19 related nervous system inflammatory diseases, with high incidence of respiratory failure and mortality. Positive SARS-CoV-2 RNA in cerebrospinal fluid of COVID-19 associated GBS patients has been rarely reported. This paper reports 4 patients with COVID-19 associated GBS in China who developed neurological symptoms 4-15 days after fever and were confirmed SARS-CoV-2 infection. All patients presented with progressive weakness of both lower limbs, 3 patients with autonomic dysfunction such as defecation and urination disorders, and 1 patient with polycranial neuritis and Miller-Fisher syndrome such as bilateral facial palsy, dysphagia, diplopia and ataxia. Nerve conduction velocity and F wave were abnormal in 3 patients, and motor conduction pathway was abnormal in 1 patient. Anti-ganglioside antibodies were tested in 3 patients, and GD1a-IgG was positive in 1 patient. All 4 patients underwent metagenomic next-generation sequencing examination in blood and cerebrospinal fluid. SARS-CoV-2 RNA was positive in blood and cerebrospinal fluid of 3 patients, and SARS-CoV-2 RNA was positive in cerebrospinal fluid of 1 patient.

Clinical analysis of 13 cases of pediatric membranous duodenal stenosis treated with endoscopic radial incision (with video) / 中华消化内镜杂志

Objective:To explore the efficacy and safety of endoscopic radial incision (ERI) for congenital membranous duodenal stenosis (MDS).Methods:The clinical data of 13 children with MDS receiving ERI in the Department of Gastroenterology of Xi'an Children's Hospital from May 2017 to December 2021 were reviewed and analyzed. The perioperative management, surgical procedures, postoperative complications and follow-up were summarized.Results:There were 5 boys and 8 girls with a median disease duration of 8 (2-20) months, and the median age of diagnosis was 13 months (5-30 months). The septum of 10 cases (10/13) was located in the descending part of the duodenum, and that of 3 cases (3/13) in the horizontal part. The papilla of 1 case (1/13) opened on the septum, that of 3 cases (3/13) within 5 cm of the mouth side of the septum, and that of 9 cases (9/13) within 5 cm of the anal side of the septum. The median diameter of the septal aperture was 3 mm (2-6 mm). All 13 children successfully underwent ERI with a median operation time of 20 min (15-32 min). The average surgical incision was 3 strokes (2-4 strokes), and the endoscope with outer diameter 9.9 mm could pass stenosis after ERI. The median incision diameter was 10 mm (10-12 mm). All patients achieved relief of clinical symptoms after ERI. One patient (1/13) suffered from the postoperative delayed bleeding, which was stopped by endoscopic titanium clamping. No intestinal perforation or duodenal papilla injury occurred, and median postoperative hospital stay was 6 days (5-10 days). The upper gastrointestinal angiogram and gastroscopy were repeated 3 months after ERI, and the median diameter of stenosis was 12 mm (10-15 mm), which was significantly dilated compared with before. The mean body weight increase at 1 month after ERI was 1.20 kg (0.50-1.80 kg), and the mean body weight increase at 3 months was 3.50 kg (2.50-4.00 kg), which reached the normal body weight of the same age.Conclusion:ERI is safe and effective for the treatment of MDS in children, and shows good clinical application and promotion value.

Effects of Bushen formulae on bone metabolism and ENaCα,NCC and ClC-3 expression in ovariectomized rats with high salt intake / 中国病理生理杂志

AIM:To investigate the effect of Bushen formulae(BHF)on bone metabolism and its possible mechanism in ovariectomized rats with high salt intake.METHODS:According to the random number table method,80 SPF-grade Sprague-Dawley rats were divided into sham group,ovariectomy(OVX)group,medium-high-salt diet(MSD)group,high-salt diet(HSD)group,BHF group,BHF with normal saline(BHF+NS)group,BHF+MSD group,and BHF+ HSD group,with 10 rats in each group.After modeling,different diets and BHF formula interventions were administered,and the concentrations of sodium chloride added to MSD group and HSD group were 2%(w/w)and 8%(w/w),respective-ly.The dose of BHF was 7.8 g·kg-1·d-1,once a day,and the treatment lasted for 12 weeks.Bone density,bone microar-chitecture,bone parameters,bone metabolism biomarkers,bone histopathological changes,the expression of epithelial sodium channel α(ENaCα),Na-Cl cotransporter(NCC),and voltage-gated chloride channel 3(ClC-3)proteins in bone tissue were detected in each group.RESULTS:Compared with sham group,the rats in OVX group had reduced bone density and destroyed bone microstructure.Compared with OVX group,the bone microstructure in MSD and HSD groups was more significantly damaged,while the levels of bone formation markers,bone glycoprotein(BGP)and type Ⅰ procolla-gen N-terminal peptide(PINP),were significantly increased in HSD group(P<0.05).Moreover,the levels of bone re-sorption markers,such as amino-terminal cross-linked telopeptides of type Ⅰ collagen(NTX),carboxy-terminal cross-linked telopeptides of type Ⅰ collagen(CTX)and tartrate-resistant acid phosphatase(TRACP),were significantly in-creased(P<0.05),indicating that bone metabolism was in high-conversion state.High-salt diet accelerated the structural destruction of bone trabeculae,and Western blot results showed that high-salt diet caused decreases in the protein expres-sion levels of ENaCα and ClC-3 and an increase in the protein expression level of NCC in femoral tissues(P<0.05).After BHF intervention,the expression of relevant ion channels caused by high salt could be regulated to different degrees.CONCLUSION:Bushen formulae could differentially regulate the expression of relevant ion channels ENaCα,ClC-3,and NCC induced by high salt to different degrees,which has certain ameliorative and therapeutic effects on the imbalance of bone metabolism.

Salvianolic Acid F Regulates Bax/Caspase-3/GSDME Signaling Pathway to Inhibit Pyroptosis of HK-2 Cells / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism of salvianolic acid F （Sal F） in repairing the high glucose-induced injury in human kidney-2 （HK-2） cells via the B-cell lymphoma-2 （Bcl-2）-associated X protein （Bax）/cysteinyl aspartate-specific proteinase 3 （Caspase-3）/gasdermin-E （GSDME） pathway. MethodThe cell counting kit-8 （CCK-8） was used to measure the relative viability of HK-2 cells exposed to high glucose and different concentrations （2.5， 5， 10， 20 μmol·L-1） of Sal F and the relative viability of HK-2 cells treated with Sal F for different time periods. The levels of lactate dehydrogenase （LDH） and interleukin-1β （IL-1β） in the supernatant of the cell culture were measured by the LDH assay kit and enzyme-linked immunosorbent assay （ELISA） kit， respectively. Flow cytometry combined with Annexin V-FITC/propidium iodide （PI） and Hoechst 33342/PI staining was employed to reveal the proportion of PI-positive HK-2 cells exposed to high glucose. Western blotting was employed to determine the protein levels of Bax， Bcl-2， cytochrome C， cysteinyl aspartate-specific proteinase （Caspase）-9， Caspase-3， and GSDME in the HK-2 cells exposed to high glucose and treated with Sal F. The 2，7-dichlorodihydrofluorescein diacetate fluorescence probe （DCFH-DA） and mitochondrial membrane potential assay kit （JC-1） were used to determine the production of reactive oxygen species （ROS） and the mitochondrial membrane potential in the HK-2 cells exposed to high glucose and treated with Sal F. ResultCompared with the blank group， the model group showed decreased cell viability （P<0.01）， elevated levels LDH and IL-1β， increased proportion of PI-positive cells （P<0.01）， up-regulated protein levels of Bax， cytochrome C， Caspase-9， Caspase-3， and GSDME （P<0.01）， down-regulated protein level of Bcl-2 （P<0.01）， decreased mitochondrial membrane potential， and excessive ROS accumulation. Compared with the model group， Sal F repaired the high glucose-induced injury in HK-2 cells （P<0.05）， lowered the levels of LDH and IL-1β （P<0.05， P<0.01）， and decreased the proportion of PI-positive cells （P<0.01）. In addition， Sal F down-regulated the protein levels of Bax， cytochrome C， Caspase-9， Caspase-3， and GSDME and up-regulated the protein level of Bcl-2 （P<0.05， P<0.01）， increased the mitochondrial membrane potential， and decreased the accumulation of ROS in HK-2 cells. ConclusionSal F can reduce the production of ROS， restore the balance of mitochondrial membrane potential， and inhibit pyroptosis via the Bax/Caspase-3/GSDME signaling pathway to repair the high glucose-induced injury in HK-2 cells.

Attention modulates early visual processing: An association between subjective contrast perception and early C1 ERP component.

The question of whether spatial attention can modulate initial afferent activity in area V1, as measured by the earliest visual event-related potential (ERP) component "C1", is still the subject of debate. Because attention always enhances behavioral performance, previous research has focused on finding evidence of attention-related enhancements in visual neural responses. However, recent psychophysical studies revealed a complex picture of attention's influence on visual perception: attention amplifies the perceived contrast of low-contrast stimuli while dampening the perceived contrast of high-contrast stimuli. This evidence suggests that attention may not invariably augment visual neural responses but could instead exert inhibitory effects under certain circumstances. Whether this bi-directional modulation of attention also manifests in C1 and whether the modulation of C1 underpins the attentional influence on contrast perception remain unknown. To address these questions, we conducted two experiments (N = 67 in total) by employing a combination of behavioral and ERP methodologies. Our results did not unveil a uniform attentional enhancement or attenuation effect of C1 across all subjects. However, an intriguing correlation between the attentional effects of C1 and contrast appearance for high-contrast stimuli did emerge, revealing an association between attentional modulation of C1 and the attentional modulation of contrast appearance. This finding offers new insights into the relationship between attention, perceptual experience, and early visual neural processing, suggesting that the attentional effect on subjective visual perception could be mediated by the attentional modulation of the earliest visual cortical response.

Sika deer velvet antler protein extract modulater bone metabolism and the structure of gut microbiota in ovariectomized mice.

Osteoporosis is a systemic osteopathy characterized by bone metabolism disorders that become more serious with age increases in postmenopausal women. Recent studies have found that antler protein is the main bioactive component of cervus pantotrichum, and it has a positive regulatory effect on bone metabolism and can improve estrogen level. This study aimed to investigate the effect of velvet antler extract (VAE) on the prevention of osteoporosis and the modulation of gut microbiota in ovariectomized (OVX) mice. OVX mice treated with 12 weeks of VAE exhibited higher levels of serum BGP, Ca2+, CT, and HyP (p < .05). Micro-CT scans showed that VAE significantly elevated bone volume fraction (BV/TV), trabecular bone number (Tb.N), trabecular bone thickness (Tb.Th), trabecular bone connection density (Conn.D), decreased trabecular separation (Tb.Sp), and structural modality index (SMI) than untreated OVX mice. The right tibial retinaculum in the VAE group was clearer, with a clearer reticular structure, smaller gaps, a tighter distribution, and a more orderly arrangement. The gut microbiota of the cecal contents was analyzed by 16 s rDNA amplicon sequencing. The data indicated that VAE modulated the species, numbers, and diversity of the gut microbiota in OVX mice. Ovariectomy caused dysbiosis of the intestinal microbiota by increasing the ratio of Firmicutes to Bacteroidetes in mice, but the ratio decreased after treatment with VAE. These results suggest that VAE has a therapeutic effect on OVX mice via modulate bone-related biochemical markers in serum and structure of gut microbiota.

Association between immune checkpoint inhibitor antitumor therapy and hepatitis B virus reactivation / 临床肝胆病杂志

In recent years, monotherapy and combination therapy with immune checkpoint inhibitors (ICIs) have achieved good efficacy in a variety of malignancies from solid tumors to lymphomas and have become a standardized and systematic treatment modality for many cancers. However, there is still a lack of studies on the safety of ICIs in hepatitis B virus (HBV)-infected patients with malignancies, and early studies have reported HBV reactivation due to ICI antitumor therapy in clinical practice. With reference to related literature, this article reviews the recent clinical trials and application of ICIs in cancer patients with chronic viral infection and clarifies the efficacy and safety of ICIs in this special population, in order to provide a reference for clinical medication.

Ketogenic diet improves low temperature tolerance in mice by up-regulating PPARα in the liver and brown adipose tissue / 生理学报

The aim of the present study was to investigate the effects of short-term ketogenic diet on the low temperature tolerance of mice and the involvement of peroxisome proliferator-activated receptor α (PPARα). C57BL/6J mice were divided into two groups: normal diet (WT+ND) group and ketogenic diet (WT+KD) group. After being fed with normal or ketogenic diet at room temperature for 2 d, the mice were exposed to 4 °C low temperature for 12 h. The changes in core temperature, blood glucose, blood pressure of mice under low temperature condition were detected, and the protein expression levels of PPARα and mitochondrial uncoupling protein 1 (UCP1) were detected by Western blot. PPARα knockout mice were divided into normal diet (PPARα-/-+ND) group and ketogenic diet (PPARα-/-+KD) group. After being fed with the normal or ketogenic diet at room temperature for 2 d, the mice were exposed to 4 °C low temperature for 12 h. The above indicators were also detected. The results showed that, at room temperature, the protein expression levels of PPARα and UCP1 in liver and brown adipose tissue of WT+KD group were significantly up-regulated, compared with those of WT+ND group. Under low temperature condition, compared with WT+ND, the core temperature and blood glucose of WT+KD group were increased, while mean arterial pressure was decreased; The ketogenic diet up-regulated PPARα protein expression in brown adipose tissue, as well as UCP1 protein expression in liver and brown adipose tissue of WT+KD group. Under low temperature condition, compared to WT+ND group, PPARα-/-+ND group exhibited decreased core temperature and down-regulated PPARα and UCP1 protein expression levels in liver, skeletal muscle, white and brown adipose tissue. Compared to the PPARα-/-+ND group, the PPARα-/-+KD group exhibited decreased core temperature and did not show any difference in the protein expression of UCP1 in liver, skeletal muscle, white and brown adipose tissue. These results suggest that the ketogenic diet promotes UCP1 expression by up-regulating PPARα, thus improving low temperature tolerance of mice. Therefore, short-term ketogenic diet can be used as a potential intervention to improve the low temperature tolerance.

Inhibition of glutaminolysis alleviates myocardial fibrosis induced by angiotensin II / 生理学报

The present study was aimed to investigate the role and mechanism of glutaminolysis of cardiac fibroblasts (CFs) in hypertension-induced myocardial fibrosis. C57BL/6J mice were administered with a chronic infusion of angiotensin II (Ang II, 1.6 mg/kg per d) with a micro-osmotic pump to induce myocardial fibrosis. Masson staining was used to evaluate myocardial fibrosis. The mice were intraperitoneally injected with BPTES (12.5 mg/kg), a glutaminase 1 (GLS1)-specific inhibitor, to inhibit glutaminolysis simultaneously. Immunohistochemistry and Western blot were used to detect protein expression levels of GLS1, Collagen I and Collagen III in cardiac tissue. Neonatal Sprague-Dawley (SD) rat CFs were treated with 4 mmol/L glutamine (Gln) or BPTES (5 μmol/L) with or without Ang II (0.4 μmol/L) stimulation. The CFs were also treated with 2 mmol/L α-ketoglutarate (α-KG) under the stimulation of Ang II and BPTES. Wound healing test and CCK-8 were used to detect CFs migration and proliferation respectively. RT-qPCR and Western blot were used to detect mRNA and protein expression levels of GLS1, Collagen I and Collagen III. The results showed that blood pressure, heart weight and myocardial fibrosis were increased in Ang II-treated mice, and GLS1 expression in cardiac tissue was also significantly up-regulated. Gln significantly promoted the proliferation, migration, mRNA and protein expression of GLS1, Collagen I and Collagen III in the CFs with or without Ang II stimulation, whereas BPTES significantly decreased the above indices in the CFs. α-KG supplementation reversed the inhibitory effect of BPTES on the CFs under Ang II stimulation. Furthermore, in vivo intraperitoneal injection of BPTES alleviated cardiac fibrosis of Ang II-treated mice. In conclusion, glutaminolysis plays an important role in the process of cardiac fibrosis induced by Ang II. Targeted inhibition of glutaminolysis may be a new strategy for the treatment of myocardial fibrosis.

Acteoside promotes autophagy and apoptosis of hepatoma cells by regulating JNK signaling pathway / 中国中药杂志

This study explored the molecular mechanism of acteoside against hepatoma 22(H22) tumor in mice through c-Jun N-terminal kinase(JNK) signaling pathway. H22 cells were subcutaneously inoculated in 50 male BALB/c mice, and then the model mice were classified into model group, low-dose, medium-dose, and high-dose acteoside groups, and cisplatin group. The administration lasted 2 weeks for each group(5 consecutive days/week). The general conditions of mice in each group, such as mental status, diet intake, water intake, activity, and fur were observed. The body weight, tumor volume, tumor weight, and tumor-inhibiting rate were compared before and after administration. Morphological changes of liver cancer tissues were observed based on hematoxylin and eosin(HE) staining, and the expression of phosphorylated(p)-JNK, JNK, B-cell lymphoma-2(Bcl-2), Beclin-1, and light chain 3(LC3) in each tissue was detected by immunohistochemistry and Western blot. qRT-PCR was performed to detect the mRNA expression of JNK, Bcl-2, Beclin-1, and LC3. The general conditions of mice in model and low-dose acteoside groups were poor, while the general conditions of mice in the remaining three groups were improved. The body weight of mice in medium-dose acteoside group, high-dose acteoside group, and cisplatin group was smaller than that in model group(P<0.01). The tumor volume in model group was insignificantly different from that in low-dose acteoside group, and the volume in cisplatin group showed no significant difference from that in high-dose acteoside group. Tumor volume and weight in medium-dose and high-dose acteoside groups and cisplatin group were lower than those in the model group(P<0.001). The tumor-inhibiting rates were 10.72%, 40.32%, 53.79%, and 56.44% in the low-dose, medium-dose, and high-dose acteoside groups and cisplatin group, respectively. HE staining showed gradual decrease in the count of hepatoma cells and increasing sign of cell necrosis in the acteoside and cisplatin groups, and the necrosis was particularly obvious in the high-dose acteoside group and cisplatin group. Immunohistochemical results suggested that the expression of Beclin-1, LC3, p-JNK, and JNK was up-regulated in acteoside and cisplatin groups(P<0.05). The results of immunohistochemistry, Western blot, and qRT-PCR indicated that the expression of Bcl-2 was down-regulated in the medium-dose and high-dose acteoside groups and cisplatin group(P<0.01). Western blot showed that the expression of Beclin-1, LC3, and p-JNK was up-regulated in acteoside and cisplatin groups(P<0.01), and there was no difference in the expression of JNK among groups. qRT-PCR results showed that the levels of Beclin-1 and LC3 mRNA were up-regulated in the acteoside and cisplatin groups(P<0.05), and the level of JNK mRNA was up-regulated in medium-dose and high-dose acteoside groups and cisplatin group(P<0.001). Acteoside promotes apoptosis and autophagy of H22 cells in mice hepatoma cells by up-regulating the JNK signaling pathway, thus inhibiting tumor growth.