Bombesin receptor subtype-3 (BRS3) is an orphan G protein-coupled receptor (GPCR) that plays critical roles in energy homeostasis, glucose metabolism, and insulin secretion. Recent structural studies have elucidated BRS3 signaling mechanisms using synthetic ligands, including BA1 and MK-5046. However, the molecular basis of BRS3 activation by bioactive natural compounds and their derivatives, particularly those derived from traditional Chinese medicine, remains unclear. Here, we present high-resolution cryogenic electron microscopy (cryo-EM) structures of the human BRS3-G_q complex in both unliganded and active states bound by two herb-derived compounds (DSO-5a and oridonin), at resolutions of 2.9, 2.8, and 2.9 Å, respectively. These structures display distinct ligand recognition patterns between DSO-5a and oridonin. Although both compounds bind to the orthosteric pocket, they differentially engage the interaction network of BRS3, as demonstrated by mutagenesis studies assessing calcium mobilization and inositol phosphate 1 (IP1) accumulation. These findings enhance our understanding of BRS3 activation and provide valuable insights into the development of small-molecule BRS3 modulators with therapeutic potential.

Aim To investigate the effect and mechanism of hydrogen molecule on myocardial injury in severe traumatic brain injury(TBI)rats.Methods Using the fluid percussion injury(FPI)-induced TBI model.72 SD rats were randomly divided into sham group,TBI group and hydrogen molecule-treated group,with 24 rats in each group,and the rats were executed at 48 h after the operation.HE staining was used to observe the myocardial injury and the in-filtration of granulocytes,ELISA was used to detect the level of superoxide dismutase(SOD),Western blot was used to de-tect the expression of inflammation-related factors myeloperoxidase(MPO)and heme oxygenase-1(HO-1)protein,RT-qPCR was used to detect the levels of cardiac troponin T(cTnT),inhibitory factor-1(IF-1),NADH/ubiquinone oxi-doreductase core subunit S7(NDUFS7),nicotinamide adenine dinucleotide phosphate(NADP)and reduced nicotinamide adenine dinucleotide phosphate(NADPH).The changes of post-traumatic echocardiography and the 7-day survival rate and body weight in the rats were observed and recorded.Results Compared with the sham group,rats in the TBI group had significantly higher troponin levels,and the echocardiographic results showed higher left ventricular end-diastolic diameter(LVEDD)and significantly lower left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),and the above pathologic changes were significantly improved after treatment with the hydrogen molecule.Myo-cardial tissue was disorganized with erythrocyte infiltration,and myocardial fibers were infiltrated with granulocytes in the section,which were improved in the hydrogen molecule-treated group.The body weight of the rats decreased dramatically after the operation,and about 5 days later dropped to the lowest level,and then showed a trend of slow recovery.mNSS scores showed that the neurological function of the rats was severely impaired after TBI,and the postoperative myocardial tissues showed an increase in the expression levels of MPO and HO-1 proteins and a decrease in the expression levels of SOD,and the above pathological changes were significantly improved by hydrogen molecule treatment.In the TBI group,the expression levels of NADPH,IF-1 and NDUFS7 were reduced,and the expression levels of the above indicators were significantly increased after hydrogen molecule treatment.Conclusion Hydrogen molecule may be able to increase mitochondrial energy metabolism in cardiomyocytes and reduce myocardial oxidative stress by synergistically enhancing the protein expression of IF-1 and NDUFS7 on the mitochondrial oxidative respiratory chain to increase cardiac function and survival rate in the acute phase of TBI.

Objective:To evaluate the clinical diagnostic significance of altered functional connectivity (FC) within the central executive network (CEN) in patients with mild cognitive impairment (MCI) related to end-stage renal disease (ESRD).Methods:A total of 155 patients with ESRD receiving hemodialysis treatment at the department of nephrology, Changzhou Second People's Hospital, from June 2020 to December 2023, were recruited. According to wether the patient had MCI symptoms, 85 patients were classified in the ESRD with MCI group, while 70 patients were in the ESRD without MCI group. Additionally, 76 healthy volunteers matched for age, sex, and years of education were enrolled in the study. All participants underwent resting-state functional magnetic resonance imaging and were evaluated using the Montreal cognitive assessment. With the dorsolateral prefrontal cortex serving the core of CEN, functional attributes of the CEN were calculated using seed-based FC analysis. Based on these imaging features and clinical data, a LASSO + Logistic regression model was constructed to predict MCI in patients with ESRD, and SPSS 20.0 software was used for analysis.Results:There were significant differences in FC in 10 brain regions, including the inferior temporal gyrus, temporal pole, corpus callosum, ventromedial prefrontal cortex, ventral posterior cingulate cortex, inferior parietal lobule, precuneus, dorsomedial prefrontal cortex, dorsal anterior cingulate cortex, and supplementary motor area, among the three groups (all P<0.001). Post hoc analysis revealed that the zFC values of the ventromedial prefrontal cortex and dorsomedial prefrontal cortex in ESRD with MCI group(0.385±0.219, 0.215±0.247) were significantly higher than those in the ESRD without MCI group (0.278±0.184, 0.121±0.221) and the healthy controls (0.206±0.217, 0.078±0.212) (all P<0.05). In addition to the ventromedial prefrontal cortex and dorsomedial prefrontal cortex, zFC values in all brain regions exhibiting significant differences were markedly reduced in both the ESRD with MCI group (temporal pole (0.157±0.221 vs 0.327±0.191), corpus callosum (0.100±0.184 vs 0.327±0.191), ventral posterior cingulate cortex (0.027±0.199 vs 0.128±0.154), inferior parietal lobule (0.218±0.195 vs 0.387±0.213), precuneus (0.193±0.184 vs 0.358±0.142), supplementary motor area (0.182±0.163 vs 0.231±0.163)) and the ESRD without MCI group (inferior temporal gyrus (0.055±0.125 vs 0.250±0.146), temporal pole (0.048±0.223 vs 0.335±0.195), corpus callosum (0.192±0.161 vs 0.327±0.191), inferior parietal lobule (0.234±0.197 vs 0.387±0.213), dorsal anterior cingulate cortex (0.383±0.242 vs 0.585±0.195), supplementary motor area (0.076±0.162 vs 0.231±0.163)), compared to healthy controls ( P<0.01). The zFC values of 4 brain regions in ESRD with MCI group were significantly higher than those in the ESRD without MCI group (inferior temporal gyrus (0.226±0.205 vs 0.055±0.125), temporal pole (0.157±0.221 vs 0.048±0.223), dorsal anterior cingulate cortex (0.498±0.254 vs 0.383±0.242), supplementary motor area (0.182±0.163 vs 0.076±0.162)) ( P<0.05). The diagnostic model developed from these results demonstrated excellent discrimination(the area under the curve=0.94, the sensitivity=0.89, the specificity=0.86, and the accuracy=0.88). Additionally, it exhibited strong calibration ( R2=0.908) and clinical applicability(patients benefited when the predicted probability exceeded 0.12). Conclusion:The enhancement of FC in CEN and its attenuation with other networks provide relevant evidence for the neuropathological mechanisms underlying MCI in patients with ESRD.The diagnostic model based on FC changes in the CEN, as presented in this study, is valuable for detecting early cognitive impairment in patients with ESRD.

Objective:To establish a solvent desorption gas chromatographymethod for the determination of phenyl glycidyl ether (PGE) .Methods:From October to December 2020, PGE in the air of workplace was collected with carbon tube and desorbed by 25% acetone-carbon disulfide. The target toxicant was separated with the gas chromatography (GC) column and analyzed with flame ionization detector (FID), and quantified by peak area.Results:The linear range of PGE in the air of workplace was 10.0-1109.0 μg/ml, the linear equation was y=1.156 x-4.328, with a correlation coefficient of 0.9997. The limit of detection was 3.0 μg/ml. The lower limit of quantification was 10.0 μg/ml. The intar-batch and inter-batch precisionswere 4.9%-6.4% and 6.2%-6.9%, respectively. The recovery rate was ranged from 97.2%-98.8%, the average collection efficiency was 100%, and the average extraction efficiency was 90.1%. The samples could be stored at 4 ℃ for 7 d. Conclusion:This method has high precision and good accuracy, and it is applicable for the determination of PGE in workplace air.

Objective:To establish a solvent desorption gas chromatographymethod for the determination of phenyl glycidyl ether (PGE) .Methods:From October to December 2020, PGE in the air of workplace was collected with carbon tube and desorbed by 25% acetone-carbon disulfide. The target toxicant was separated with the gas chromatography (GC) column and analyzed with flame ionization detector (FID), and quantified by peak area.Results:The linear range of PGE in the air of workplace was 10.0-1109.0 μg/ml, the linear equation was y=1.156 x-4.328, with a correlation coefficient of 0.9997. The limit of detection was 3.0 μg/ml. The lower limit of quantification was 10.0 μg/ml. The intar-batch and inter-batch precisionswere 4.9%-6.4% and 6.2%-6.9%, respectively. The recovery rate was ranged from 97.2%-98.8%, the average collection efficiency was 100%, and the average extraction efficiency was 90.1%. The samples could be stored at 4 ℃ for 7 d. Conclusion:This method has high precision and good accuracy, and it is applicable for the determination of PGE in workplace air.

Objective To investigate the effect of hypercapnia on hypoxic-ischemic brain injury in rats.Methods Forty-eight adult male SD rats were randomly divided into three groups: sham group (group S), hypoxic ischemic group (group HI) and hypercapnia group (group HP), n=16 in each group.Levine`s model was used to cause hypoxic-ischemic brain injury.In group S, the left common carotid artery was separated without ligation for 1 h, then ventilation with air maintaining the normal levels of PaO2 and PaCO2 for 3 h.In group HI, the left common carotid artery was separated and ligated for 1 h, PaO2 was maintained at 30-49 mm Hg by ventilating with low concentration (11%-13%) O2 for 3 hours.Based on group HI, PaCO2 in group HP was maintain at 60-80 mm Hg by inhalation of mixture gas containing (11%-13%) O2-8%CO2-N2 for 3 hours.FITC-dextran was used to measure the permeability of blood-brain barrier, TUNEL staining were used to observe the changes in the structure of the cerebral cortex.The expressions of aquaporin AQP4 and RECA-1 in cerebral cortex were detected by immunofluorescence and western blot.Results The level of brain water content, permeability of blood brain barrier and AQP4 expression were significantly increased in group HP as compared with group S and group HI (P<0.05).The histopathologic damage,as well as neuronal apoptotic index were aggravated in group HP as compared with group HI (P<0.05).Conclusion Hypercapnia may aggravate the brain damage during severe hypoxic-ischemic brain injury.This may associate with the increased expression AQP4 and the damage of blood-brain barrier.

Objective To analyze the musculoskeletal injuries related to touch screen VDT operation and design implications.Methods The effects of touch screen size and angles on touch-screen-VDT-operation-related muscle load and fatigue were explored using thorough experiment and EMG acquisition method,and the independent variables included the size and angle and the dependant variables consisted of the load and fatigue of flexor digitorum superficialis (FDS),extensor digitorum communis (EDC),extensor carpi radialis (ECR) and extensor carpi ulnaris (ECU).Results No significant difference was found with regard to pointing success rate and accuracy at all screen sizes and angles levels.FDS and EDC MVC％ increased with increasing touch screen size at all levels of angles.FDS MVC％ decreased while EDC MVC％ increased with inclining angles at all levels of touch screen sizes.All measured muscles' MF did not decrease with time.Conclusion This study helps to provide basis for the optimization of equipment design,reduce exposure to musculoskeletal injuries risks and implement primary prevention.

OBJECTIVE:To provide reference for the patent application of artificial cultivation and seed treatment technology of Paridis Rhizoma and natural resources protection. METHODS:Retrieved from State Intellectual Property Office patent database,“Paridis Rhizoma”and“Paris polyphylla”were used as search keywords from 1985 to March 31,2015;Paridis Rhizoma cultiva-tion and seed treatment technology patents as research object were analyzed in fields of the amount of patent application,regional construction and legal status,etc. RESULTS:Among 54 Paridis Rhizoma cultivation patent application,there were 19 applications from Yunnan,9 from Sichuan,8 from Hubei,5 from Anhui,4 from Hunan,3 from Guizhou,2 from Jiangxi,1 from Fujian, Shanxi,Jiangsu,Guangxi respectively;there were 18 licensed patents,and 13 licensed patents maintained more than 3 years, among which 1 patent right transferred;from aspect of patent without right,6 patent right were given up due to fail to pay annual fee,1 rejected and 5 withdrawn;from main types of patent proposer,enterprise submitted 24 patent application,universities 15, scientific research institutes 8 and other 7. 24 enterprise patents involved 21 enterprises,indicating that patent protection net didn’t form due to disperse proposers. CONCLUSIONS:Patent application is mainly from Yunnan. There still are some problems,such as small number of patent applications,poor quality of application writing,little patent transformation. It is suggested to plan artificial cultivation technology,enhance the quality of patent application,pay attention to patent operation and achievement transformation and other measures,in order to protect Paridis Rhizoma resource and industrial development.

OBJECTIVETo establish a gas chromatography method for determination of methyl propyl ketone in the air of workplace.

METHODSMethyl propyl ketone in the air of workplace was collected with activated carbon tubes and desorbed with carbon disulfide before sample loading. The target toxicant was separated with the capillary column and detected with a hydrogen flame ionization detector, identified by retention time, and quantified by peak area.

RESULTSThe linear range of methyl propyl ketone in the air of workplace was 202.5∼4 860.0 µg/ml, with a correlation coefficient of 0.999 98. The limit of detection was 1.5 µg/ml. The lower limit of quantification was 5.0 µg/ml. The minimum detectable concentration was 1.0 mg/m(3) under 1.5 L sampling volume and 1.0 ml desorption solution volume. The relative standard deviation of different methyl propyl ketone concentrations was 1.42%∼1.65%, and the recovery rate was 94.9%∼ 97.9%.

CONCLUSIONThis method has high sensitivity, precision, and accuracy, and it is applicable for determination of methyl propyl ketone in the air of workplace.

Air ; analysis ; Air Pollutants, Occupational ; analysis ; Carbon Disulfide ; Chromatography, Gas ; methods ; Pentanones ; analysis ; Workplace

Adult ; Air Pollutants, Occupational ; adverse effects ; Health Status ; Humans ; Male ; Middle Aged ; Occupational Exposure ; adverse effects ; Toluene 2,4-Diisocyanate ; adverse effects ; Young Adult