Type 2 diabetes (T2D) is an independent risk factor for cognitive impairment. The dysregulation of hypoxia inducible factor (HIF) signaling in T2D patients results in impaired adaptive responses to hypoxia, thereby accelerating the progression of complications. However, limited knowledge is available regarding its precise function in diabetes-associated cognitive impairment (DACI). Here, elevated HIF-1α levels were observed in brain endothelial cells (ECs) of db/db mice. Functionally, brain ECs-specific knockdown of H if1 a significantly ameliorated T2D-induced memory loss and neuronal damage. Glycolysis in brain ECs was inhibited in this process, as indicated by RNA-seq, leading to decreased hippocampal lactate production through reduced LDHA expression. Notably, T2D patients showed increased cerebrospinal fluid lactate levels, which were strongly associated with their cognitive dysfunction. Intrahippocampal injection of lactate accelerated cognitive dysfunction and impaired adult hippocampal neurogenesis (AHN) in db/db mice. Conversely, reducing hippocampal lactate levels through the intrahippocampal injection of oxamate delayed the onset of memory deficits. Furthermore, asiatic acid was discovered to protect db/db mice from cognitive impairment by decreasing brain endothelial HIF-1α expression and subsequently reducing hippocampal lactate-induced AHN damage. Overall, this study elucidates the inhibiting role played by endothelial HIF-1α-driven lactate in AHN and highlights a potential tactic of targeting HIF-1α in brain ECs for treating cognitive impairment.

Excavating the quantitative trait locus (QTL) associated with rice cooking quality, analyzing candidate genes, and improving cooking quality-associated traits of rice varieties by genetic breeding can effectively improve the taste of rice. In this study, we used the indica rice HZ, the japonica rice Nekken2 and 120 recombinant inbred lines (RILs) populations constructed from them as experimental materials to measure the gelatinization temperature (GT), gel consistency (GC) and amylose content (AC) of rice at the maturity stage. We combined the high-density genetic map for QTL mapping. A total of 26 QTLs associated with rice cooking quality (1 QTL associated with GT, 13 QTLs associated with GC, and 12 QTLs associated with AC) were detected, among which the highest likelihood of odd (LOD) value reached 30.24. The expression levels of candidate genes in the localization interval were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), and it was found that the expression levels of six genes were significantly different from that in parents. It was speculated that the high expression of LOC_Os04g20270 and LOC_Os11g40100 may greatly increase the GC of rice, while the high expression of LOC_Os01g04920 and LOC_Os02g17500 and the low expression of LOC_Os03g02650 and LOC_Os05g25840 may reduce the AC. The results lay a molecular foundation for the cultivation of new high-quality rice varieties, and provide important genetic resources for revealing the molecular regulation mechanism of rice cooking quality.
Quantitative Trait Loci ; Oryza/genetics* ; Plant Breeding ; Cooking ; Genetic Association Studies

To evaluate the feasibility and safety of suprapubic three-arm robot-assisted laparoscopic radical prostatectomy (STA-RLRP). Fifteen patients with prostatic cancer underwent STA-RLRP. All the 15 procedures were completed successfully, without the need for ancillary trocars or additional instruments. No patient required conversion to standard laparoscopy or open surgery. STA-RLRP is feasible and safe with good short-term tumor control, satisfactory recovery of urinary control function and good cosmetic outcome, which is worthy of clinical application.

Objective:To summarize the clinical features of children with pneumonia caused by coinfection of human adenovirus type 7 and Mycoplasma pneumoniae.Methods:A total of 36 children with pneumonia caused by coinfection of human adenovirus type 7 and Mycoplasma pneumoniae (coinfection group) diagnosed in the Wuhan Children′s Hospital from December 1, 2018 to September 1, 2019 were enrolled.Their clinical manifestations, laboratory examinations, and imaging findings were retrospectively analyzed.In the same period, 94 children with single human adenovirus type 7 infection pneumonia were selected as the single infection group.Differences between 2 groups were compared using the Student′s t-test, rank sum test and Chi- square test. Results:In the coinfection group, 25 cases were males, 11 cases were females, their mean age was 3.11 years.The main clinical manifestations included fever (97.2%) and cough (100.0%). The mean body temperature was 40.0 ℃, with the thermal peak of 4 times per day, and the mean course of fever of 11 days.The incidence of severe pneumonia was significantly higher in coinfection group (86.1%) than that of single infection group (69.1%) ( χ2=3.878, P<0.05). The common complications included myocardial damage (55.5%), heart failure (16.7%), liver function damage (25.0%), gastrointestinal bleeding (5.5%), toxic encephalopathy (11.0%), hemophagocytic syndrome (16.7%), and bronchiolitis obliterans (50.0%). The levels of cytokines like interleukin (IL)-6 [237.84(108.59, 606.36) ng/L], IL-10[31.44(12.13, 69.60) ng/L]and interferon-γ [(102.85±92.23) ng/L] were obviously elevated, and among them, IL-6 and IL-10 elevations were significantly pronounced in coinfection group than that of single infection group[148.35(57.43, 390.82); 19.67(10.96, 35.35)] ( Z=-1.984, -2.077, all P<0.05). Lung consolidation (50.0%) and pleural effusion (38.9%) were common in coinfection group, and the incidence of pleural effusion in coinfection group was significantly higher than that of single infection group (19.1%)( χ2=5.594, P<0.05). Conclusions:Most of the pneumonia caused by human adenovirus type 7 mixed Mycoplasma pneumoniae in children is severe pneumonia, which may be related to the cytokine storm.