Inherited OKT4 epitope deficiency in a Chinese rhesus macaque.

OKT4 is an important epitope of the CD4 molecular. Amino acid mutations in the CD4V3 region result in deficiency of the OKT4 epitope in human. Here, we firstly reported a case of hereditary deficiency of OKT4 epitope in an inbred Chinese rhesus macaque family. This epitope deficiency is due to cytosine to thymine transition and homozygote at the nucleotide position 793 of CD4 coding sequences, which leads to the replace of arginine at 265th position of CD4 molecule by tryptophan. The results reveal that OKT4 epitope deficiency is a very old phenotype and may be parentally inherited, and emphasize the importance of avoiding inbreeding in primate population breeding.

Abnormality of anxious behaviors and functional connectivity between the amygdala and the frontal lobe in maternally deprived monkeys.

OBJECTIVE: Anxious behaviors often occur in individuals who have experienced early adversity. Anxious behaviors can bring many hazards, such as social withdrawal, eating disorders, negative self-efficacy, self-injurious thoughts and behaviors, anxiety disorders, and even depression. Abnormal behavior are is closely related to changes in corresponding circuit functions in the brain. This study investigated the relationship between brain circuits and anxious behaviors in maternal-deprived rhesus monkey animal model, which mimic early adversity in human. METHODS: Twenty-five rhesus monkeys (Macaca mulatta) were grouped by two different rearing conditions: 11 normal control and mother-reared (MR) monkeys and 14 maternally deprived and peer-reared (MD) monkeys. After obtaining images of the brain areas with significant differences in maternal separation and normal control macaque function, the relationship between functional junction intensity and stereotypical behaviors was determined by correlation analysis. RESULTS: The correlation analysis revealed that stereotypical behaviors were negatively correlated with the coupling between the left lateral amygdala subregion and the left inferior frontal gyrus in both MD and MR macaques. CONCLUSION: This study suggests that early adversity-induced anxious behaviors are associated with changes in the strength of the amygdala-prefrontal connection. The normalization of the regions involved in the functional connection might reverse the behavioral abnormality. It provides a solid foundation for effective intervention in human early adversity. SIGNIFICANCE STATEMENT: This study suggests that early adversity-induced anxious behaviors are associated with changes in the strength of the amygdala-prefrontal connection. The higher the amygdala-prefrontal connection strength, the less stereotyped behaviors exhibited by monkeys experiencing early adversity. Thus, in the future, changing the strength of the amygdala-prefrontal connection may reverse the behavioral abnormalities of individuals who experience early adversity. This study provides a solid foundation for effective intervention in humans' early adversity.

Aging induces severe SIV infection accompanied by an increase in follicular CD8+ T cells with overactive STAT3 signaling.

The number of elderly people living with HIV is increasing globally, and the condition of this population is relatively complicated due to the dual effects of aging and HIV infection. However, the impact of HIV infection combined with aging on the immune homeostasis of secondary lymphoid organs remains unclear. Here, we used the simian immunodeficiency virus mac239 (SIVmac239) strain to infect six young and six old Chinese rhesus macaques (ChRMs) and compared the infection characteristics of the two groups in the chronic stage through multiplex immunofluorescence staining of lymph nodes. The results showed that the SIV production and CD4/CD8 ratio inversion in old ChRMs were more severe than those in young ChRMs in both the peripheral blood and the lymph nodes, especially when a large number of CD8+ T cells infiltrated the follicles and germinal centers. STAT3 in these follicular CXCR5+CD8+ T cells was highly activated, with high expression of granzyme B, which might be caused by the severe inflammatory milieu in the follicles of old ChRMs. This study indicates that aging may be a cofactor involved in SIV-induced immune disorders in secondary lymphoid tissues, affecting the effective antiviral activity of highly enriched follicular CXCR5+CD8+ cells.

Infection with novel coronavirus (SARS-CoV-2) causes pneumonia in Rhesus macaques.

The 2019 novel coronavirus (SARS-CoV-2) outbreak is a major challenge for public health. SARS-CoV-2 infection in human has a broad clinical spectrum ranging from mild to severe cases, with a mortality rate of ~6.4% worldwide (based on World Health Organization daily situation report). However, the dynamics of viral infection, replication and shedding are poorly understood. Here, we show that Rhesus macaques are susceptible to the infection by SARS-CoV-2. After intratracheal inoculation, the first peak of viral RNA was observed in oropharyngeal swabs one day post infection (1 d.p.i.), mainly from the input of the inoculation, while the second peak occurred at 5 d.p.i., which reflected on-site replication in the respiratory tract. Histopathological observation shows that SARS-CoV-2 infection can cause interstitial pneumonia in animals, characterized by hyperemia and edema, and infiltration of monocytes and lymphocytes in alveoli. We also identified SARS-CoV-2 RNA in respiratory tract tissues, including trachea, bronchus and lung; and viruses were also re-isolated from oropharyngeal swabs, bronchus and lung, respectively. Furthermore, we demonstrated that neutralizing antibodies generated from the primary infection could protect the Rhesus macaques from a second-round challenge by SARS-CoV-2. The non-human primate model that we established here provides a valuable platform to study SARS-CoV-2 pathogenesis and to evaluate candidate vaccines and therapeutics.

Direct sunlight exposure reduces hair cortisol levels in rhesus monkeys (Macaca mulatta).

Major depressive disorder (MDD), commonly known as depression, is a mental disease characterized by a core symptom of low mood. It lasts at least two weeks (Badamasi et al., 2019; Wang et al., 2019) and is frequently accompanied by low self-esteem, loss of interest in routinely enjoyable activities, low energy, and unexplained pain (Huey et al., 2018; Park et al., 2012; Post & Warden, 2018; Rice et al., 2019; Xiao et al., 2018). Approximately 2%-8% of adults with MDD commit suicide (Richards & O'Hara, 2014; Strakowski & Nelson, 2015), and around half of suicidal individuals suffer depression or other mood disorders (Bachmann, 2018).

[Three-dimensional spatial measurement versus conventional CT planning in laparoscopic partial nephrectomy for renal tumors].

OBJECTIVE: To analyze the advantages of spatial measurement of anatomical parameters in a 3D model in surgical planning for laparoscopic partial nephrectomy (LPN). METHODS: From February, 2016 to October, 2017, 37 patients diagnosed with T1 renal mass underwent LPN based on 3D reconstruction after enhanced CT scanning using the Uromedix-3D system (group A), and another 38 patients received LPN with conventional CT planning (group B). The anatomical parameters were measured in the reconstructed 3D model and the demographic data, surgical outcome and postoperative data were compared between the two groups. RESULTS: In group A, the average time for 3D model reconstruction was (29.3∓9.7) min; the length, width and depth of the renal defect in 3D model were 3.2∓1.1 cm, 2.6∓0.9 cm and 1.7∓0.7 cm, respectively; The distance of the tumor from the collecting system was 3.8∓2.2 mm; The mean R.E.N.A.L score of the patients was 7∓1.5, and 3 patients had accessory renal artery and 2 had early branching of the renal artery. LPNs were completed via the retroperitoneal approach in all the 75 patients without conversion to open or total nephrectomy. Group A and group B showed significant differences in warm ischemic time (26.7∓6.4 vs 31.9∓7.0 min), tumor-excision time (8.4∓2.6 vs 10.4∓2.8 min), renal defect suture time (18.3∓3.9 vs 21.5∓3.4 min), 24-h volume of retroperitoneal drainage (88.6∓40.2 vs 134.3∓58.3 mL) and 48-h volume of retroperitoneal drainage (127.9∓54.5 vs 198.1∓86.3 mL), but not in the demographic data, operation time, intraoperative blood loss or postoperative hospital stay. CONCLUSIONS: 3D reconstruction of the renal masses can be completed efficiently and accurately using this system. Compared with conventional CT-based measurement, 3D spatial measurement of the anatomical structures helps to increase the precision in the performance of LPN and reduce the warm ischemia time.

[Small RNA interference-mediated ADP-ribosylation factor 6 silencing inhibits proliferation, migration and invasion of human prostate cancer PC-3 cells].

OBJECTIVE: To investigate the effects of silencing ADP-ribosylation factor 6 (Arf6) on the proliferation, migration, and invasion of prostate cancer cell line PC-3 and the possible molecular mechanisms. METHODS: Three Arf6-specific small interfering RNA (siRNA) were transfected into cultured prostate cancer cell line PC-3. Arf6 expression was examined by real-time PCR and Western blotting. MTT assay, wound healing assay, and Transwell migration and invasion assay were used to observe the effect of Arf6 silencing on the proliferation, migration, and invasion ability of PC-3 cells. The levels of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), ERK1/2, p-AKT, AKT and Rac1 were detected by Western blotting. RESULTS: Transfection of siRNA-3 resulted in significantly decreased Arf6 mRNA and protein expression with inhibition rates of (91.88±3.13)% and (86.37±0.57)%, respectively. Arf6 silencing by siRNA-3 markedly suppressed the proliferation, migration and invasion of PC-3 cells and reduced the expression levels of p-ERK1/2 and Rac1. CONCLUSION: Silencing of Arf6 efficiently inhibits the proliferation, migration, and invasion of PC-3 cells in vitro, and the underlying mechanisms may involve the down-regulation of p-ERK1/2 and Rac1.