HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Objective:To observe the changes of plasma nitric oxide (NO) and desmosine (DES) concentrations in animals under different decompression pressure loads, and to explore the role of NO and DES in quantitative evaluation of diving decompression injury.Methods:A total of 50 male SD rats were divided into five groups with 10 rats in each group by the random table method. Rats in Group 1 were not pressurized and were given air ventilation, and left the cabin after 120 min; after pressurized to 70 m for 70 min, 40 rats in the other four groups were decompressed at a constant rate to the normal pressure in 40 min (Group 2), 30 min (Group 3), 20 min (Group 4) and 10 min (Group 5), respectively. The changes of plasma NO and DES concentrations in rats after leaving the cabin were observed. A total of 40 male rabbits were divided into four groups with 10 rabbits in each group by the random table method. The rabbits were used to simulate fast buoyancy ascent escape from the depth of 150 m and the compression pressure doubled every four seconds. The four groups were decompressed at a constant rate of 6 m/s after being given different bottom time, i. e., 4 s (Group 1), 60 s (Group 2), 180 s (Group 3), and 300 s (Group 4). The changes of plasma NO and DES concentrations in the rabbits after leaving the cabin were analyzed.Results:Compared with the rats in the Group 1, the plasma NO and DES concentrations of the rats of the Group 5 significantly increased, with statistically significant differences ( P<0.05 or P<0.01), and the plasma DES concentration of the rats in the Group 4 also increased, with a statistically significant difference ( P<0.05). The plasma NO and DES concentrations in rats were positively correlated with the reciprocal of the decompression time at a constant rate (NO: r=0.683, P<0.01; DES: r=0.535, P<0.01) and showed significant linear regression relationships (NO: r2=0.467, P<0.01; DES: r2=0.287, P<0.01). Compared with the values before escape, the plasma NO concentrations in the rabbits of the Group 3 and 4 increased significantly, with statistically significant differences ( P<0.01), and the plasma DES concentrations in all four rabbit groups increased significantly, with statistically significant differences ( P<0.01). After leaving the cabin, compared with the rabbits in the Group 1, the plasma NO and DES concentrations in rabbits of the Group 3 and 4 increased significantly, with statistically significant differences (NO: P<0.05 or P<0.01; DES: P<0.01). After leaving the cabin, the plasma NO and DES concentrations in rabbits were positively correlated with the bottom time (NO: r=0.672, P<0.01; DES: r=0.702, P<0.01)and showed significant linear relationships (NO: r2=0.452, P<0.01; DES: r2=0.493, P<0.01). Conclusion:The plasma NO and DES concentrations can quantitatively indicate the damage caused by decompression pressure loads, which makes it possible to design decompression protocol and safety evaluation. The severity of decompression injuries is linearly related to the reciprocal of decompression time (or rate) that determines the decompression pressure load, which have reference value for the decompression rate control in the theoretical model of decompression.

Objective:To observe the changes of plasma nitric oxide (NO) and desmosine (DES) concentrations in animals under different decompression pressure loads, and to explore the role of NO and DES in quantitative evaluation of diving decompression injury.Methods:A total of 50 male SD rats were divided into five groups with 10 rats in each group by the random table method. Rats in Group 1 were not pressurized and were given air ventilation, and left the cabin after 120 min; after pressurized to 70 m for 70 min, 40 rats in the other four groups were decompressed at a constant rate to the normal pressure in 40 min (Group 2), 30 min (Group 3), 20 min (Group 4) and 10 min (Group 5), respectively. The changes of plasma NO and DES concentrations in rats after leaving the cabin were observed. A total of 40 male rabbits were divided into four groups with 10 rabbits in each group by the random table method. The rabbits were used to simulate fast buoyancy ascent escape from the depth of 150 m and the compression pressure doubled every four seconds. The four groups were decompressed at a constant rate of 6 m/s after being given different bottom time, i. e., 4 s (Group 1), 60 s (Group 2), 180 s (Group 3), and 300 s (Group 4). The changes of plasma NO and DES concentrations in the rabbits after leaving the cabin were analyzed.Results:Compared with the rats in the Group 1, the plasma NO and DES concentrations of the rats of the Group 5 significantly increased, with statistically significant differences ( P<0.05 or P<0.01), and the plasma DES concentration of the rats in the Group 4 also increased, with a statistically significant difference ( P<0.05). The plasma NO and DES concentrations in rats were positively correlated with the reciprocal of the decompression time at a constant rate (NO: r=0.683, P<0.01; DES: r=0.535, P<0.01) and showed significant linear regression relationships (NO: r2=0.467, P<0.01; DES: r2=0.287, P<0.01). Compared with the values before escape, the plasma NO concentrations in the rabbits of the Group 3 and 4 increased significantly, with statistically significant differences ( P<0.01), and the plasma DES concentrations in all four rabbit groups increased significantly, with statistically significant differences ( P<0.01). After leaving the cabin, compared with the rabbits in the Group 1, the plasma NO and DES concentrations in rabbits of the Group 3 and 4 increased significantly, with statistically significant differences (NO: P<0.05 or P<0.01; DES: P<0.01). After leaving the cabin, the plasma NO and DES concentrations in rabbits were positively correlated with the bottom time (NO: r=0.672, P<0.01; DES: r=0.702, P<0.01)and showed significant linear relationships (NO: r2=0.452, P<0.01; DES: r2=0.493, P<0.01). Conclusion:The plasma NO and DES concentrations can quantitatively indicate the damage caused by decompression pressure loads, which makes it possible to design decompression protocol and safety evaluation. The severity of decompression injuries is linearly related to the reciprocal of decompression time (or rate) that determines the decompression pressure load, which have reference value for the decompression rate control in the theoretical model of decompression.

AIM: To explore the molecular mechanism of brain tissue injury induced by lipopolysaccharide(LPS),the effects of panaxadiol(PDS) on the expression of nuclear factor kappa B(NF-?B) in cerebral cortex of rat with LPS shock were studied.METHODS: Rats were randomly divided into LPS group,LPS+dexamethasone group,LPS+PDS group and control group.The DNA binding activity and protein expression of NF-?B were observed.These indices were assayed at 1 h and 4 h after intravenous injection of LPS(4 mg?kg-1).RESULTS: EMSA showed that PDS inhibited NF-?B DNA-binding activity in nuclear extracts at both 1 h and 4 h after LPS injection,compared with the LPS group(P