TRiC/CCT chaperonin is required for the folding and inhibitory effect of WDTC1 on adipogenesis.

Obesity has become a global pandemic. WDTC1 is a WD40-containing protein that functions as an anti-obesity factor. WDTC1 inhibits adipogenesis by working as an adaptor of the CUL4-DDB1 E3 ligase complex. It remains unclear about how WDTC1 is regulated. Here, we show that the TRiC/CCT functions as a chaperone to facilitate the protein folding of WDTC1 and proper function in adipogenesis. Through tandem purification, we identified the molecular chaperone TRiC/CCT as WDTC1-interacting proteins. WDTC1 bound the TRiC/CCT through its ADP domain, and the TRiC/CCT recognized WDTC1 through the CCT5 subunit. Disruption of the TRiC/CCT by knocking down CCT1 or CCT5 led to misfolding and lysosomal degradation of WDTC1. Furthermore, the knockdown of CCT1 or CCT5 eliminated the inhibitory effect of WDTC1 on adipogenesis. Our studies uncovered a critical role of the TRiC/CCT in the folding of WDTC1 and expanded our knowledge on the regulation of adipogenesis.

Robotic versus laparoscopic total mesorectal excision for rectal cancer: a meta-analysis of long-term survival and urogenital functional outcomes.

INTRODUCTION: Robotic surgical technology has been widely introduced and applied in various fields of surgery. The aim of this study was to analyze long-term oncological and urogenital functional outcomes following laparoscopic/robotic total mesorectal excision (TME) in rectal cancer surgery. EVIDENCE ACQUISITION: We identified studies that compared oncological and functional outcomes following laparoscopic TME (LTME) and robotic TME (RTME) for treatment of rectal cancer over the past 16 years. Data related to overall survival (OS), disease-free survival (DFS), International Prostate Symptom Score (IPSS), and International Index of Erectile Function (IIEF) were subjected to meta-analysis. EVIDENCE SYNTHESIS: There was no difference in long-term OS and DFS in the pooled data. Compared with LTME, there were significant differences in the score of IPSS at 3, 6 and 12 months for RTME, in the pooled data for male patients. There were significant differences in IIEF score for male patients at 3 and 6 months. CONCLUSIONS: Compared with LTME, RTME has better preservation of urinary and sexual functions and comparable long-term oncological outcome in rectal cancer.

Duodenal perforation after organophosphorus poisoning: A case report.

BACKGROUND: Organophosphorus poisoning (OP) is one of the common critical conditions in emergency departments in China, which is usually caused by suicide by taking oral drugs. Patients with severe OP have disturbance of consciousness, respiratory failure, toxic shock, gastrointestinal dysfunction, and so on. As far as we know, the perforation of the duodenum caused by OP has not been reported yet. CASE SUMMARY: A 33-year-old male patient suffered from acute severe OP, associated with abdominal pain. Multiple computed tomography scans of the upper abdomen showed no evidence of intestinal perforation. However, retrograde digital subtraction angiography, performed via an abdominal drainage tube, revealed duodenal perforation. After conservative treatment, the symptoms eased and the patient was discharged from hospital. CONCLUSION: Clinicians should pay close attention to gastrointestinal dysfunction and abdominal signs in patients with severe OP. If clinical manifestation and vital signs cannot be explained by common complications, stress duodenal ulcer or perforation should be highly suspected.

DDB1 binds histone reader BRWD3 to activate the transcriptional cascade in adipogenesis and promote onset of obesity.

Obesity has become a global pandemic. Identification of key factors in adipogenesis helps to tackle obesity and related metabolic diseases. Here, we show that DDB1 binds the histone reader BRWD3 to promote adipogenesis and diet-induced obesity. Although typically recognized as a component of the CUL4-RING E3 ubiquitin ligase complex, DDB1 stimulates adipogenesis independently of CUL4. A DDB1 mutant that does not bind CUL4A or CUL4B fully restores adipogenesis in DDB1-deficient cells. Ddb1+/- mice show delayed postnatal development of white adipose tissues and are protected from diet-induced obesity. Mechanistically, by interacting with BRWD3, DDB1 is recruited to acetylated histones in the proximal promoters of ELK1 downstream immediate early response genes and facilitates the release of paused RNA polymerase II, thereby activating the transcriptional cascade in adipogenesis. Our findings have uncovered a CUL4-independent function of DDB1 in promoting the transcriptional cascade of adipogenesis, development of adipose tissues, and onset of obesity.

OsTMF attenuates cold tolerance by affecting cell wall properties in rice.

Plant cell wall composition and structure can be modified as plants adapt to environmental stresses; however, the underlying regulatory mechanisms remain elusive. Here, we report that OsTMF, a homologue of the human TATA modulatory factor (TMF) in rice (Oryza sativa) and highly conserved in plants, negatively regulates cold tolerance through modification of cell wall properties. Cold stress increased the expression of OsTMF and accumulation of OsTMF in the nucleus, where OsTMF acts as a transcription activator and modulates the expression of genes involved in pectin degradation (OsBURP16), cellulose biosynthesis (OsCesA4 and OsCesA9), and cell wall structural maintenance (genes encoding proline-rich proteins and peroxidases). OsTMF directly activated the expression of OsBURP16, OsCesA4, and OsCesA9 through binding to the TATA cis-elements in their promoters. Under cold stress conditions, OsTMF negatively regulated pectin content and peroxidase activity and positively regulated cellulose content, causing corresponding alterations to cell wall properties, all of which collectively contribute to the negative effect of OsTMF on cold tolerance. Our findings unravel a previously unreported molecular mechanism of a conserved plant TMF protein in the regulation of cell wall changes under cold stress.

Genetic control of the root system in rice under normal and drought stress conditions by genome-wide association study.

A variety of adverse conditions including drought stress severely affect rice production. Root system plays a critical role in drought avoidance, which is one of the major mechanisms of drought resistance. In this study, we adopted genome-wide association study (GWAS) to dissect the genetic basis controlling various root traits by using a natural population consisting of 529 representative rice accessions. A total of 413 suggestive associations, containing 143 significant associations, were identified for 21 root traits, such as maximum root length, root volume, and root dry weight under normal and drought stress conditions at the maturation stage. More than 80 percent of the suggestive loci were located in the region of reported QTLs for root traits, while about 20 percent of suggestive loci were novel loci detected in this study. Besides, 11 reported root-related genes, including DRO1, WOX11, and OsPID, were found to co-locate with the association loci. We further proved that the association results can facilitate the efficient identification of causal genes for root traits by the two case studies of Nal1 and OsJAZ1. These loci and their candidate causal genes provide an important basis for the genetic improvement of root traits and drought resistance.

RNA-Seq identifies key reproductive gene expression alterations in response to cadmium exposure.

Cadmium is a common toxicant that is detrimental to many tissues. Although a number of transcriptional signatures have been revealed in different tissues after cadmium treatment, the genes involved in the cadmium caused male reproductive toxicity, and the underlying molecular mechanism remains unclear. Here we observed that the mice treated with different amount of cadmium in their rodent chow for six months exhibited reduced serum testosterone. We then performed RNA-seq to comprehensively investigate the mice testicular transcriptome to further elucidate the mechanism. Our results showed that hundreds of genes expression altered significantly in response to cadmium treatment. In particular, we found several transcriptional signatures closely related to the biological processes of regulation of hormone, gamete generation, and sexual reproduction, respectively. The expression of several testosterone synthetic key enzyme genes, such as Star, Cyp11a1, and Cyp17a1, were inhibited by the cadmium exposure. For better understanding of the cadmium-mediated transcriptional regulatory mechanism of the genes, we computationally analyzed the transcription factors binding sites and the mircoRNAs targets of the differentially expressed genes. Our findings suggest that the reproductive toxicity by cadmium exposure is implicated in multiple layers of deregulation of several biological processes and transcriptional regulation in mice.