Recently, photodynamic therapy (PDT) has gained considerable attention as a promising therapeutic approach for the treatment of psoriasis. Unfortunately, the activation of high mobility group box 1 protein (HMGB1) by PDT triggers innate and adaptive immune responses, which exacerbate skin inflammation. Herein, we combined glycyrrhizic acid (GA), a natural anti-inflammatory compound and immunomodulator derived from the herb Glycyrrhiza uralensis Fisch., with PDT actuated by the photosensitizer chlorin e6 (Ce6) by co-loading them in GA-based lipid nanoparticles coated with a catechol-modified quaternary chitosan salt (GC NPs/QCS-C). GC NPs/QCS-C exhibited high drug loading efficacy, uniform size distribution, an ideal topical adhesive property, enhanced skin retention and penetration in psoriasis-like lesions, and high intracellular uptake in epidermal cells compared with the counterparts. Subsequently, the transdermal administration of GC NPs/QCS-C followed by near-infrared laser radiation in an imiquimod-induced psoriasis-like mouse model significantly ameliorated psoriasis symptoms, promoted the apoptosis of hyperproliferative epidermal cells, and alleviated the inflammatory cascade. The significant therapeutic outcomes of GC NPs/QCS-C were attributed to the synergistic effects of GA and PDT on modulating immune cell recruitment and inhibiting dendritic cell maturation. Our results demonstrated that the topical bio-adhesive nanosystem that combines GA and Ce6 offers a synergistic chemo-phototherapeutic strategy for psoriasis treatment.

Objective:To develop one kind of alarm system with pressure sensor,so as to prevent compression injuries of patients with upper limb dysfunction due to the movement of the examination bed during computed tomography(CT)examination.Methods:The alarm system with pressure sensor was constructed on the basis of Arduino UNO open-source main control board and the HX711 weighing module.The Arduino E3 power supply module was used to provide power for system,and ESP8266 main control board was used to realize remote alarm,and its 3 dimension(3D)printed customized shell can directly be installed at the edge of examination bed.A total of 228 patients with upper limb dysfunction who underwent CT examination at Xianxian County Hospital of TCM during July 2022 and October 2022 were selected.They were randomly divided into observation group and control group by using a computer-generated random number sequence.The observation group was monitored for possibly potential compression risks on upper limb of patients by using the alarm system with pressure sensor.The patients of control group were respectively accompanied by one accompanying personnel to go into the scanning room,and they wore lead aprons,lead skirts,and other protective appliances for radiation protection.When a patient is found to be at risk of being crushed,an alarm should be raised by calling a halt.The valid alarm rates of the two alarm methods were calculated.Results:There were 37 times of alarm in observation group in examination,and 31 times were valid alarms and 6 times were invalid alarms in them.In control group,there were 49 times of alarm from accompanying personnel,and 29 times were valid alarms and 20 times were invalid alarms in 49 times of alarm.The valid alarm rate of observation group was significantly higher than that of control group,and the difference was statistically significant(x2=6.048,P<0.05).Conclusion:The installation of alarm system with pressure sensor is easy,and its use is convenient,and it has a higher valid alarm rate during CT examination,and it can effectively protect patients to prevent compression injuries.

This study collected data on 9 cases of fatal head injuries caused by adjustable wrenches and analyzed 16 types of injury characteristics of head injuries caused by adjustable wrenches.The distinctive patterns of head injuries caused by adjustable wrenches were summarized.A four level scoring model and scoring criteria were constructed for head injuries caused by adjustable wrenches.From a morphological perspective,it provided a reference for the inference of injury-causing instruments in forensic practice.

Objective:To develop one kind of alarm system with pressure sensor,so as to prevent compression injuries of patients with upper limb dysfunction due to the movement of the examination bed during computed tomography(CT)examination.Methods:The alarm system with pressure sensor was constructed on the basis of Arduino UNO open-source main control board and the HX711 weighing module.The Arduino E3 power supply module was used to provide power for system,and ESP8266 main control board was used to realize remote alarm,and its 3 dimension(3D)printed customized shell can directly be installed at the edge of examination bed.A total of 228 patients with upper limb dysfunction who underwent CT examination at Xianxian County Hospital of TCM during July 2022 and October 2022 were selected.They were randomly divided into observation group and control group by using a computer-generated random number sequence.The observation group was monitored for possibly potential compression risks on upper limb of patients by using the alarm system with pressure sensor.The patients of control group were respectively accompanied by one accompanying personnel to go into the scanning room,and they wore lead aprons,lead skirts,and other protective appliances for radiation protection.When a patient is found to be at risk of being crushed,an alarm should be raised by calling a halt.The valid alarm rates of the two alarm methods were calculated.Results:There were 37 times of alarm in observation group in examination,and 31 times were valid alarms and 6 times were invalid alarms in them.In control group,there were 49 times of alarm from accompanying personnel,and 29 times were valid alarms and 20 times were invalid alarms in 49 times of alarm.The valid alarm rate of observation group was significantly higher than that of control group,and the difference was statistically significant(x2=6.048,P<0.05).Conclusion:The installation of alarm system with pressure sensor is easy,and its use is convenient,and it has a higher valid alarm rate during CT examination,and it can effectively protect patients to prevent compression injuries.

This study collected data on 9 cases of fatal head injuries caused by adjustable wrenches and analyzed 16 types of injury characteristics of head injuries caused by adjustable wrenches.The distinctive patterns of head injuries caused by adjustable wrenches were summarized.A four level scoring model and scoring criteria were constructed for head injuries caused by adjustable wrenches.From a morphological perspective,it provided a reference for the inference of injury-causing instruments in forensic practice.

Objective:To discusses the variations of 7Be, 137Cs and 210Pb activity concentrations in the air in Beijing from March 16, 2021 to March 31, 2023, and their correlation with temperature, precipitation, relative humidity, barometric pressure, PM10 (only limited to 137Cs) and other meteorological parameters. Methods:A total of 60 aerosol samples were collected using the HRHA01-SFS1000/A ultra-large flowair sampler in the automatic radiation monitoring station. The activity concentrations of 7Be, 137Cs and 210Pb in the aerosol samples were measured by GMX-60 low background anti-Compton high purity germanium gamma spectrometer. Pearson correlation coefficient was used to show the correlation of the relevant parameters. Results:The seasonal mean values of 7Be activity concentration were spring 4.31 mBq/m 3, summer 3.53 mBq/m 3, autumn 3.09 mBq/m 3 and winter 2.45 mBq/m 3, respectively, ranging from 1.17 to 7.79 mBq/m 3, with the overall mean of (3.36±1.33) mBq/m 3. The activity concentration of 137Cs ranged from 0.39 to 8.49 μBq/m 3, with an average of (0.59±1.47) μBq/m 3. The average activity concentrations of 210Pb were spring 0.53 mBq/m 3, summer 0.44 mBq/m 3, autumn 0.72 mBq/m 3 and winter 0.75 mBq/m 3, respectively, ranging from 0.21 to 1.36 mBq/m 3, with an average of (0.56±0.26) mBq/m 3. The activity concentration of 7Be was correlated with temperature and pressure ( r=0.38, -0.40), the activity concentration of 137Cs was correlated with precipitation ( r=-0.41), and the activity concentration of 210Pb was correlated with temperature and pressure ( r=-0.31, 0.37). The variation of 137Cs activity concentration in the air showed an obvious seasonal pattern, and the peak value generally appears in spring of each year (March to May), which was related to the frequent spring dust in Beijing. The activity concentration of 210Pb in the air was affected by coal combustion heating in winter, and has a peak value during November to March. Conclusions:The activity concentrations of 7Be, 137Cs and 210Pb in the air in Beijing are within the normal range, showing a seasonal trend.

Lipophagy, the selective engulfment of lipid droplets (LDs) by autophagosomes for lysosomal degradation, is critical to lipid and energy homeostasis. Here we show that the lipid transfer protein ORP8 is located on LDs and mediates the encapsulation of LDs by autophagosomal membranes. This function of ORP8 is independent of its lipid transporter activity and is achieved through direct interaction with phagophore-anchored LC3/GABARAPs. Upon lipophagy induction, ORP8 has increased localization on LDs and is phosphorylated by AMPK, thereby enhancing its affinity for LC3/GABARAPs. Deletion of ORP8 or interruption of ORP8-LC3/GABARAP interaction results in accumulation of LDs and increased intracellular triglyceride. Overexpression of ORP8 alleviates LD and triglyceride deposition in the liver of ob/ob mice, and Osbpl8-/- mice exhibit liver lipid clearance defects. Our results suggest that ORP8 is a lipophagy receptor that plays a key role in cellular lipid metabolism.
Animals ; Mice ; Lipid Droplets ; Autophagy ; Autophagosomes ; Homeostasis ; Triglycerides

Bacterial antitumor therapy has great application potential given its unique characteristics, including genetic manipulation, tumor targeting specificity and immune system modulation. However, the nonnegligible side effects and limited efficacy of clinical treatment limit their biomedical applications. Engineered bacteria for therapeutic applications ideally need to avoid their accumulation in normal organs and possess potent antitumor activity. Here, we show that macrophage-mediated tumor-targeted delivery of Salmonella typhimurium VNP20009 can effectively reduce the toxicity caused by administrating VNP20009 alone in a melanoma mouse model. This benefits from tumor-induced chemotaxis for macrophages combined with their slow release of loaded strains. Inspired by changes in the tumor microenvironment, including a decrease in intratumoral dysfunctional CD8⁺ T cells and an increase in PDL1 on the tumor cell surface, macrophages were loaded with the engineered strain VNP-PD1nb, which can express and secrete anti-PD1 nanoantibodies after they are released from macrophages. This novel triple-combined immunotherapy significantly inhibited melanoma tumors by reactivating the tumor microenvironment by increasing immune cell infiltration, inhibiting tumor cell proliferation, remodeling TAMs to an M1-like phenotype and prominently activating CD8⁺ T cells. These data suggest that novel combination immunotherapy is expected to be a breakthrough relative to single immunotherapy.

Objective:To investigate the role and mechanism of sodium valproate (VPA) in cardiac and cerebral injuries after cardiopulmonary resuscitation (CPR) in pigs.Methods:Twenty-five healthy male domestic pigs, weighing (37±3) kg, were randomly divided into the sham group ( n=6), CPR group ( n=10), and CPR+VPA group ( n=9). Cardiac arrest was induced by alternating current delivered via a pacing catheter in the right ventricle and untreated for 9 min, and then CPR was performed for 6 min, in which this procedure was used to establish the animal model of cardiac arrest and CPR. At 5 min after resuscitation, a dose of 150 mg/kg of VPA was infused with a pump via the femoral vein in 1 h in the CPR+VAP group. At 1 h, 2 h, 4 h and 24 h after resuscitation, blood samples were drawn from the femoral vein, and then used to measure the serum concentrations of cardiac troponin I (cTnI), creatine kinase MB (CKMB), neuron specific enolase (NSE), and S100B protein (S100B) by ELISA. At 24 h after resuscitation, the animals were euthanized, and then tissue specimens in the left myocardium and brain cortex were rapidly harvested to detect the expression levels of C/EBP homologous protein (CHOP), caspase 12, and caspase 3 by Western blot, and the rate of apoptotic cells was detected by TUNEL. Continuous variables were compared with one way analysis of variance among the three groups. Results:(1) After resuscitation, cardiac and cerebral injury biomarkers including cTnI, CKMB, NSE, and S100B in serum were significantly increased in the CPR and CPR+VPA groups compared with the Sham group (all P<0.05). The serum concentrations of cTnI and NSE starting 1 h after resuscitation and the serum concentrations of CKMB and S100B starting 2 h after resuscitation were significantly decreased in the CPR+VPA group compared to the CPR group (all P<0.05). (2) Those proteins related to cell apoptosis mediated by endoplasmic reticulum stress, including CHOP, caspase 12, and caspase 3, were significantly increased, and meanwhile apoptosis index was markedly elevated after resuscitation in the CPR and CPR+VPA groups compared with the Sham group (all P<0.05). Nevertheless, the expression levels of CHOP, caspase 12, and caspase 3 were significantly decreased, and cell apoptosis was markedly reduced in the heart and brain after resuscitation in the CPR+VPA group compared to the CPR group (all P<0.05). Conclusions:VPA can alleviate cardiac and cerebral injuries after CPR in pigs, and its mechanism may be possibly related to the inhibition of cell apoptosis mediated by endoplasmic reticulum stress.

Objective To evaluate the feasibility, efficacy and safety of new nano material occluder of single rivet type (left-disk with no-hub) in treating ventricular septal defect (VSD) in order to provide experimental basis for clinical application. Methods A total of 26 healthy adult dogs were selected for this study . Under thoracotomy , VSD model was established through fluoroscopically-guided percutaneous puncturing of the right ventricular free wall. The models were randomly and equally divided into the study group(n=13, using nano material VSD occluder) and the control group(n=13, using double-hub nitinol occluder). Every two dogs from each group were sacrificed each time at one, 2, and 3 months after percutaneous closure of VSD with corresponding occluder, the tissue samples were collected and sent for gross examination as well as for the optical and electronic microscopy study;the blood concentration of nickel ion was also determined. The state of endothelialization after implantation of the new type occluder was evaluated, and the complications such as residual shunt and superficial thrombus formation were recorded. The results were analyzed. Results By open chest operation with small incision and percutaneous puncturing of the right ventricular free wall, VSD model was successfully established in all 26 dogs. The success rate of the implantation of the VSD occluder in the study group was 100%, while it was 91.7% in the control group. One, 2, 3 and 6 months after the implantation, the heart specimens of 25 dogs were removed and gross examination showed that neither occluder displacement nor alloy wire fracture occurred in both groups. No thrombus formation or vegetation attached on the disk surface was observed. One month after the procedure , in the study group the bilateral disk surfaces of the occluder were covered with thin layer transparent tissue , which were proved to be composed of the fibrous tissue and endothelial cells through pathologic and electronic microscopy study. Six months after implantation, the superficial tissue of the occluder became further thickened and the occluder edge became fused with the surrounding heart tissue. Conclusion The design of the new VSD nano materials occluder, which has a left-disk with no hub, is very scientific. Compared with double-hub nitinol occluder, the new device can shorten the time of complete endothelialization and effectively occlude the VSD. Therefore, this new nano material occluder has promising prospect in clinical application.