Characterization and Crystal Structures of a Cubebol-Producing Sesquiterpene Synthase from Antrodia cinnamomea.

Antrodia cinnamomea is an endemic species found in Taiwan, known for its medicinal properties in treating various discomforts, including inflammation, diarrhea, abdominal pain, and other diseases. A. cinnamomea contains terpenoids that exhibit numerous bioactivities, making them potential food additives. This discovery piqued our interest in uncovering their biosynthetic pathway. Herein, we conducted functional and structural characterization of a sesquiterpene synthase Cop4 from A. cinnamomea (AcCop4). Through gas chromatography-mass spectrometry analysis, we observed that AcCop4 catalyzes the cyclization of farnesyl pyrophosphate (FPP), primarily producing cubebol. Cubebol is widely used as a long-lasting cooling and refreshing agent in the food industry. The structure of AcCop4, complexed with pyrophosphate and magnesium ions, revealed the closure of the active site facilitated by R311. Interestingly, binding of pyrophosphate and magnesium ions did not cause any significant conformational change in the G1/2 helix of AcCop4, indicating that the apo form is not fully open. This high-resolution structure serves as a solid basis for understanding the biosynthetic mechanism of AcCop4 and supports further production and modification of cubebol for its applications in the food industry.

Genome Sequence of Cluster BI1 Streptomyces griseus Phage TaidaOne.

Bacteriophage TaidaOne was isolated from soil collected in Taipei, Taiwan, using the host Streptomyces griseus. It is a siphovirus with a 56,183-bp genome that contains 86 protein-coding genes. Based on gene content similarity, it was assigned to actinobacteriophage subcluster BI1, within which only TaidaOne and GirlPower genomes contain an acetyltransferase homolog gene.

Structural, Biophysical, and Biochemical Elucidation of the SARS-CoV-2 Nonstructural Protein 3 Macro Domain.

The pandemic outbreak of a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has threatened the global public health and economy since late December 2019. SARS-CoV-2 encodes the conserved macro domain within nonstructural protein 3, which may reverse cellular ADP-ribosylation and potentially cut the signal of a viral infection in the cell. Herein, we report that the SARS-CoV-2 macro domain was examined as a poly-ADP-ribose (ADPR) binding module and possessed mono-ADPR cleavage enzyme activity. After confirming the ADPR binding ability via a biophysical approach, the X-ray crystal structure of the SARS-CoV-2 macro domain was determined and structurally compared with those of other viruses. This study provides structural, biophysical, and biochemical bases to further evaluate the role of the SARS-CoV-2 macro domain in the host response via ADP-ribose binding but also as a potential target for drug design against COVID-19.

Expressions of Sry-related High Mobility Group Box 9 and Gastrokine-1 in Gastric Cancer and Their Relationships with Prognosis / 中国医学科学院学报

Objective To explore the expressions of Sry-related high mobility group box 9(SOX9)and gastrokine-1(GKN1) in gastric cancer tissues and their relationships with clinicopathologic features and prognosis of patients.Methods Immunohistochemistry was used to detect the expressions of SOX9 and GKN1 in 70 cases of gastric cancer tissues and corresponding paracancerous tissues including 27 cases of intestinal metaplasia and 43 cases of normal gastric mucosa. The relationships of SOX9 and GKN1 expressions with clinicopathological features and prognosis were analyzed in gastric cancer tissues.Results The high expression rates of SOX9 in gastric cancer tissues,intestinal metaplasia,and normal gastric mucosa were 92.9%(65/70),77.8%(21/27),and 55.8%(24/43),respectively(=21.722,<0.001). Positive nuclear and cytoplasmic staining was observed. The high nuclear expression rate of SOX9 in gastric cancer tissues was 67.1%,which was significantly higher than those of intestinal metaplasia(37.0%,=0.007)and normal gastric mucosa(23.3%,<0.001). The high cytoplasmic expression rate of GKN1 in normal gastric mucosa was 76.7%,which was significantly higher than those of intestinal metaplasia(44.4%,=0.006)and gastric cancer tissues(37.1%,<0.001). Univariate analysis demonstrated that the nuclear expression of SOX9 in gastric cancer was associated with the degree of tissue differentiation(=0.007),while the cytoplasmic expression of GKN1 was associated with both the degree of tissue differentiation(=0.002)and whether the pathological type was a signet-ring cell carcinoma(=0.009). Furthermore,the nuclear expression of SOX9 was negatively correlated with the expression of GKN1 in gastric cancer(=15.424,<0.001). The 5-year survival rates of patients with high or low nuclear expression of SOX9 were 33.8% and 67.5%,respectively(=0.016).The 5-year survival rates of patients with high or low expression of GKN1 were 60.0% and 35.6%,respectively(=0.044). Further research indicated that 5-year survival rate of patients with high nuclear expression of SOX9 and low expression of GKN1 was 28.8%. Cox multivariate regression analysis showed that TNM stage(stage Ⅱ:=7.435,95%:1.313-42.096,=0.023;stage Ⅲ:=12.214,95%:2.677-55.721,=0.001)and nuclear expression level of SOX9(=3.297,95%:1.199-9.065,=0.021)were independent risk factors for the prognosis of gastric cancer patients.Conclusions Changes in the expressions of SOX9 and GKN1 may be associated with the malignant biological behavior of gastric cancer. SOX9 may be a potential prognostic factor. The combined detection of SOX9 and GKN1 expression and the further study of their molecular mechanism may provide new clues for early diagnosis,targeted therapy,and prognostic prediction of gastric cancer.

Therapeutic effect of vadian neurectomy under the nasal endoscope on the vasomotor rhinitis / 中南大学学报(医学版)

OBJECTIVE@#To explore the therapeutic effect of vadian neurectomy under the nasal endoscope on the vasomotor rhinitis.@*METHODS@#Anatomic measurements of vadian canal in 14 cadavers were carried out, and vadian neurectomy under the nasal endoscope was performed on 51 patients with vasomotor rhinitis.@*RESULTS@#Anatomic measurements showed vadian canal was located behind the sphenoid-palatine hole, and its external orifice was shaped as infundibular. The vertical diameter was (3.5+/-0.9) mm and the horizontal diameter was (2.9+/-0.5) mm. The distance to the rotundum foramen and nasal septum was (6.1+/-1.2) mm and (10.5+/-5.9) mm. Longitudinal axes of the vadian canal was (27.0+/-9.6) degrees with the horizontal plane, and (7.8+/-2.5) degree with the sagittal plane. Among the 51 patients, 41(80.4%) patients showed complete response and 3(5.9%) partial response at the 5-year follow-up.@*CONCLUSION@#Vadian neurectomy under nasal endoscope is an effective technique for vasomotor rhinitis.

Genomic instability in nasopharyngeal carcinoma / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the effect of genomic instability on prognostics in nasopharyngeal carcinoma.@*METHODS@#Genomic instability was assessed by inter-simple sequence repeats polymerase chain reaction (inter-SSR PCR) in 38 patients with nasopharyngeal carcinoma. Characterization and verification of band alterations shared in different tumors were carried out by sequencing and nest PCR.@*RESULTS@#Thirty-one (81.6%) of the 38 patients showed genomic altercations, and genomic instability index ranged 0 to 16.2 percent. A gain-based genomic damage shared in 6 tumors was identified on chromosome 6q27. Genomic alteration was significantly more in patients less than 5-year survival than those with more than 5-year survival (P<0.05).@*CONCLUSION@#Genomic instability can be an early event marker in carcinogenesis of nasopharyngeal carcinoma. Aggravation of genomic alterations is a poor prognosis for cancer recovery.