Porcine hemagglutinating encephalomyelitis virus(PHEV)is one of the coronaviruses susceptible to swine populations.The non-structural protein 2(NS2)encoded by its genome is fre-quently deleted during the epidemic transmission of the virus,but its biological significance re-mains unclear.In order to explore the structure and function of the NS2 protein,this study utilized platforms such as ProtParam,TMHMM,NetPhos3.1,and ExPASy to analyze its physicochemical properties,spatial structure,genetic evolution,and post-translational modification characteristics.Meanwhile,the NS2 protein was expressed in eukaryotes and transcriptome sequencing was per-formed to clarify the biological processes it participates in.The results showed that the NS2 protein consists of 233 amino acids,with a molecular weight of 26.735 kDa,and a half-life of approximately 30 hours in mammals.It includes 13 phosphorylation sites,2 N-glycosylation sites,and 1 O-glyco-sylation site,with no signal peptide and strong hydrophilicity.The a-helix accounts for the highest proportion in NS2(43.78％),followed by random coils(36.05％).The homology of the NS2 pro-tein between the epidemic strains PHEV-CC14 and PHEV-JL/2008 in Northeast China is 99.57％.The NS2 protein is widely involved in the regulation of nerve-related functions,such as axon guid-ance and synaptic development.This study preliminarily clarified the biological function of the NS2 protein,providing a new perspective for understanding the pathogenic mechanism of PHEV.

Aim To investigate the therapeutic effects of a newly developed Tadalafil tablets on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,as well as its influence on the activation of the NF-κB signaling pathway in myo-cardial cells.Methods SD rats were randomly divid-ed into 4 groups:the sham operation group(Sham),the model group(AAC),the tadalafil new tablet treat-ment group(N-Tad,5 mg·kg-1),and the positive control drug treatment group(Cialis,10 mg·kg-1g).The AAC model group and treatment group rats under-went blunt dissection and constrictive ligation of the abdominal aorta at the left renal artery branch point during surgery,while the Sham group rats only had their arteries separated without any constrictive liga-tion.Rats in the treatment groups received either N-Tad or Cialis via gavage three days after modeling,while rats in the sham group and the model group re-ceived physiological saline daily for 8 weeks.Small an-imal ultra-high-resolution echocardiography and hemo-dynamic assessment were applied to evaluate left ven-tricular function in each group of rats,and the calcula-tion of the left ventricular mass index was conducted.By employing Western blot and RT-PCR.we assessed the impact of this treatment on the expression of the hy-pertrophy factor atrial natriuretic peptide(ANP),phosphorylated NF-κB p65 protein(p-NF-κB p65),and phosphorylated IκB-α in the left heart tissue of rats and in H9c2 cardiomyocytes.Results Compared to the Sham group,the AAC rats exhibited a significant decrease in left heart function,an increase in left ven-tricular mass index,and a notable increase in ANP and p-p65 expression in the left heart tissue(P＜0.05).Both N-Tad and Cialis treatments could significantly enhance left ventricular function,decrease left ventric-ular mass index,and inhibit the expression of ANP and phosphorylated NF-κB p65 in rats with myocardial hy-pertrophy(P＜0.05).Notably,the therapeutic effect of low-dose N-Tad was comparable to that of high-dose Cialis.At the cellular level,Tadalafil significantly in-hibited the activation of the NF-κB signaling pathway and reduced the expression of associated proteins in H9c2 cardiomyocytes.Conclusions N-Tad can sig-nificantly inhibit p65 and IκB-α phosphorylation,and the activation of the NF-κB signaling pathway,reduce ANP expression,and improve pathological myocardial hypertrophy,as well as mitigate left heart function damage caused by abdominal aortic constriction.

Aim To investigate the therapeutic effects of a newly developed Tadalafil tablets on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,as well as its influence on the activation of the NF-κB signaling pathway in myo-cardial cells.Methods SD rats were randomly divid-ed into 4 groups:the sham operation group(Sham),the model group(AAC),the tadalafil new tablet treat-ment group(N-Tad,5 mg·kg-1),and the positive control drug treatment group(Cialis,10 mg·kg-1g).The AAC model group and treatment group rats under-went blunt dissection and constrictive ligation of the abdominal aorta at the left renal artery branch point during surgery,while the Sham group rats only had their arteries separated without any constrictive liga-tion.Rats in the treatment groups received either N-Tad or Cialis via gavage three days after modeling,while rats in the sham group and the model group re-ceived physiological saline daily for 8 weeks.Small an-imal ultra-high-resolution echocardiography and hemo-dynamic assessment were applied to evaluate left ven-tricular function in each group of rats,and the calcula-tion of the left ventricular mass index was conducted.By employing Western blot and RT-PCR.we assessed the impact of this treatment on the expression of the hy-pertrophy factor atrial natriuretic peptide(ANP),phosphorylated NF-κB p65 protein(p-NF-κB p65),and phosphorylated IκB-α in the left heart tissue of rats and in H9c2 cardiomyocytes.Results Compared to the Sham group,the AAC rats exhibited a significant decrease in left heart function,an increase in left ven-tricular mass index,and a notable increase in ANP and p-p65 expression in the left heart tissue(P＜0.05).Both N-Tad and Cialis treatments could significantly enhance left ventricular function,decrease left ventric-ular mass index,and inhibit the expression of ANP and phosphorylated NF-κB p65 in rats with myocardial hy-pertrophy(P＜0.05).Notably,the therapeutic effect of low-dose N-Tad was comparable to that of high-dose Cialis.At the cellular level,Tadalafil significantly in-hibited the activation of the NF-κB signaling pathway and reduced the expression of associated proteins in H9c2 cardiomyocytes.Conclusions N-Tad can sig-nificantly inhibit p65 and IκB-α phosphorylation,and the activation of the NF-κB signaling pathway,reduce ANP expression,and improve pathological myocardial hypertrophy,as well as mitigate left heart function damage caused by abdominal aortic constriction.

Porcine hemagglutinating encephalomyelitis virus(PHEV)is one of the coronaviruses susceptible to swine populations.The non-structural protein 2(NS2)encoded by its genome is fre-quently deleted during the epidemic transmission of the virus,but its biological significance re-mains unclear.In order to explore the structure and function of the NS2 protein,this study utilized platforms such as ProtParam,TMHMM,NetPhos3.1,and ExPASy to analyze its physicochemical properties,spatial structure,genetic evolution,and post-translational modification characteristics.Meanwhile,the NS2 protein was expressed in eukaryotes and transcriptome sequencing was per-formed to clarify the biological processes it participates in.The results showed that the NS2 protein consists of 233 amino acids,with a molecular weight of 26.735 kDa,and a half-life of approximately 30 hours in mammals.It includes 13 phosphorylation sites,2 N-glycosylation sites,and 1 O-glyco-sylation site,with no signal peptide and strong hydrophilicity.The a-helix accounts for the highest proportion in NS2(43.78％),followed by random coils(36.05％).The homology of the NS2 pro-tein between the epidemic strains PHEV-CC14 and PHEV-JL/2008 in Northeast China is 99.57％.The NS2 protein is widely involved in the regulation of nerve-related functions,such as axon guid-ance and synaptic development.This study preliminarily clarified the biological function of the NS2 protein,providing a new perspective for understanding the pathogenic mechanism of PHEV.

Lancang-Mekong Cooperation is a new type of subregional cooperation mechanism initiated and built by China and other five countries of the Lancang-Mekong subregion, namely Laos, Myanmar, Thailand, Cambodia, and Vietnam. Countries in the Lancang-Mekong subregion are geographically and culturally connected, and they have nurtured their unique traditional medicine. By combing the history of traditional medicine exchanges between China and other Lancang-Mekong countries and their progress of modern research, this paper summarized the challenges and opportunities of traditional medicine cooperation in the Lancang-Mekong subregion. It has been found that many regional cooperation mechanisms coexist for a long time in the Lancang-Mekong subregion and the medicinal resources are abundant. However, the degree of their development and utilization varies, and modern scientific research is insufficient. Lancang-Mekong Cooperation has provided a strong support for integrating the advantageous resources in Lancang-Mekong subregion countries and making progress together. Focusing on the development and protection of medicinal resources, this paper puts forward a new path of cooperation in the intellectual property rights and characteristic seed resource protection, the compilation of universal herbal pharmacopoeia in various countries, the research and development of public health products, and the construction of traditional herbal industry bases, thus enabling the traditional medicine to better protect the public health and building a human health community.
China ; Humans ; Materia Medica ; Medicine, Traditional ; Rivers ; Thailand

Sterol-regulatory element binding proteins (SREBPs) are the key transcriptional regulators of lipid metabolism. The activation of SREBP requires translocation of the SREBP precursor from the endoplasmic reticulum to the Golgi, where it is sequentially cleaved by site-1 protease (S1P) and site-2 protease and releases a nuclear form to modulate gene expression. To search for new genes regulating cholesterol metabolism, we perform a genome-wide CRISPR/Cas9 knockout screen and find that partner of site-1 protease (POST1), encoded by C12ORF49, is critically involved in the SREBP signaling. Ablation of POST1 decreases the generation of nuclear SREBP and reduces the expression of SREBP target genes. POST1 binds S1P, which is synthesized as an inactive protease (form A) and becomes fully mature via a two-step autocatalytic process involving forms B'/B and C'/C. POST1 promotes the generation of the functional S1P-C'/C from S1P-B'/B (canonical cleavage) and, notably, from S1P-A directly (non-canonical cleavage) as well. This POST1-mediated S1P activation is also essential for the cleavages of other S1P substrates including ATF6, CREB3 family members and the α/β-subunit precursor of N-acetylglucosamine-1-phosphotransferase. Together, we demonstrate that POST1 is a cofactor controlling S1P maturation and plays important roles in lipid homeostasis, unfolded protein response, lipoprotein metabolism and lysosome biogenesis.

Objective To investigate the effect of cysteine protease inhibitor derived from S chistosoma japonicum(SjCys-tatin)on dextran sodium sulfate(DSS)-induced acute ulcerative colitis in mice.Methods Eighteen C57BL/6 mice were ran-domly divided into three groups:a control group treated with PBS(Group A),a DSS-induced-colitis group treated with PBS(Group B),and a DSS-induced-colitis group treated with SjCystatin(Group C).Colitis was induced in mice by giving 3％DSS orally for 7 days.During this period,the mice were daily injected with 10&mu;g of SjCystatin or PBS only as a control intraperitone-ally.The mice were monitored daily for their clinical manifestations and given scores based on disease activity index(DAI).The severity of colonic inflammation was monitored by the macroscopic score and pathological change.The cytokine profile including TNF-α,IL-4,IL-6 and IL-10 in the supernatants of colon homogenate was detected by ELISA.Results Compared with Group A(0.50 ± 0.28),the DAI score increased significantly in Group B(9.30 ± 1.30)(F=86.86,P<0.01),with remarkable path-ological damages seen in colon tissues.and the levels of TNF-α and IL-6 were(321.33±67.01)and(403.58 ±180.51)pg/mL.The DAI score significantly reduced in Group C(6.67±1.57)as compared to Group B(F=86.86,P<0.01),with improve-ments in the macroscopic and microscopic pathology in mouse colon specimens.As compared to Group B,the levels of TNF-α [(188.14 ± 40.14)pg/mL] and IL-6 [(209.71 ± 48.47)pg/mL] significantly decreased(F=17.46 and 9.89,both P<0.01).Con-clusion SjCystatin has a significantly inhibitory effect for alleviating DSS-induced acute ulcerative colitis in C57BL/6 mice.

ObjectiveTo improve the accuracy of prostate cancer (PCa) detection by focusing biopsy on the suspected lesion manifested by MRI with the total number of biopsy cores relatively unchanged.

METHODSA prospective randomized analysis was performed on 262 cases of suspected PCa detected by multi-parametric MRI (mp-MRI), each with a single suspected lesion with 10 &mu;g/L≤ PSA <20 &mu;g/L. All the patients underwent targeted transrectal prostate biopsy guided by fusion imaging of MRI with transrectal ultrasonography (TRUS), using the 6X+6 strategy (6 cores in the suspected region and another 6 in the systematic prostate) for 134 cases and the traditional 12+2X method (12 cores in the systematic prostate and 2 in the suspected region) for the other 128. Comparisons were made between the two methods in the PCa detection rate in the cases of suspected lesion, total PCa detection rate, incidence of post-biopsy complications, and Gleason scores. Analyses were performed on the prostate imaging reporting and data system (PI-RADS) score, location, transverse section, and diameter of the suspected lesion.

RESULTSBoth the total PCa detection rate and that in the cases of suspected lesion were significantly higher in the 6X+6 (44.8% and 37.3%) than in the 12+2X group (37.5% and 27.3%) (P<0.05). MRI showed that the suspected lesions were mostly (45%) located in the middle part of the prostate, the mean area of the transverse section was (0.48±0.11) cm2, and the mean diameter of the tumor was (8.51±2.21) mm. The results of biopsy showed that low-grade tumors (Gleason 3+3=6) accounted for 68% in the 6X+6 group and 71% in the 12+2X group. No statistically significant differences were found between the two groups in the incidence rate of post-biopsy complications.

CONCLUSIONSCompared with the traditional 12+2X method, for the suspected lesion manifested by mp-MRI, focusing biopsy on the suspected region with the 6X+6 strategy can achieve a higher PCa detection rate without increasing the incidence of complications.

Humans ; Image-Guided Biopsy ; methods ; Magnetic Resonance Imaging ; methods ; Magnetic Resonance Imaging, Interventional ; Male ; Neoplasm Grading ; Prospective Studies ; Prostate ; diagnostic imaging ; pathology ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; blood ; diagnostic imaging ; pathology