Expression of bone morphogenetic protein 4 (BMP4) in adipocytes of white adipose tissue (WAT) produces "white adipocytes" with characteristics of brown fat and leads to a reduction of adiposity and its metabolic complications. Although BMP4 is known to induce commitment of pluripotent stem cells to the adipocyte lineage by producing cells that possess the characteristics of preadipocytes, its effects on the mature white adipocyte phenotype and function were unknown. Forced expression of a BMP4 transgene in white adipocytes of mice gives rise to reduced WAT mass and white adipocyte size along with an increased number of a white adipocyte cell types with brown adipocyte characteristics comparable to those of beige or brite adipocytes. These changes correlate closely with increased energy expenditure, improved insulin sensitivity, and protection against diet-induced obesity and diabetes. Conversely, BMP4-deficient mice exhibit enlarged white adipocyte morphology and impaired insulin sensitivity. We identify peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1α) as the target of BMP signaling required for these brown fat-like changes in WAT. This effect of BMP4 on WAT appears to extend to human adipose tissue, because the level of expression of BMP4 in WAT correlates inversely with body mass index. These findings provide a genetic and metabolic basis for BMP4's role in altering insulin sensitivity by affecting WAT development.oth white adipose tissue (WAT) and brown adipose tissue (BAT) function in the energy homeostasis of humans and other mammals. WAT stores energy in form of triglycerides during periods of excessive caloric intake for later use when energy demand exceeds intake (1). In contrast, brown adipose tissue (BAT) uses "stored triglycerides" to generate energy in the form of heat, most notably when environmental temperature falls (2).The excessive accumulation of body fat in WAT is the result of both hypertrophy and hyperplasia of white adipocytes (3). Such changes give rise to insulin resistance, type-2 diabetes, and an inflammatory response, thus implicating white adipocytes in the etiology of these conditions (4, 5). In contrast, promotion of BAT activities helps prevent genetic obesity, insulin resistance, and diabetes (6).Unlike the expansive mass of brown adipocytes in the interscapular region, brown adipose tissue mass in the normal adult human is proportionally smaller and previously was believed to be functionally less important. Recently, however, by using [18F]-2-fluoro-D-2-deoxy-D-glucose PET, metabolically active regions were detected in the cervical, supraclavicular, axillary, and paravertebral regions of adult human subjects (7-9). The metabolically active areas were found to consist of an admixture of brown-like adipocytes in WAT (10) which increase dramatically following cold exposure or treatment with antidiabetic drugs, thiazolidinediones, or adrenergic activators (11-13). These cells recently have been designated as "beige" (14) or "brite" (15, 16) cells derived from ...

Tamm-Horsfall protein (THP) is a glycoprotein normally targeted to the apical membrane domain of the kidney's thick ascending limbs (TAL). We previously showed that THP of TAL confers protection to proximal tubules against acute kidney injury (AKI) via a possible cross talk between the two functionally distinct tubular segments. However, the extent, timing, specificity, and functional effects of basolateral translocation of THP during AKI remain unclear. Using an ischemia-reperfusion (IRI) model of murine AKI, we show here that, while THP expression in TAL is downregulated at the peak of injury, it is significantly upregulated 48 h after IRI. Confocal immunofluorescence and immunoelectron microscopy reveal a major redirection of THP during recovery from the apical membrane domain of TAL towards the basolateral domain, interstitium, and basal compartment of S3 segments. This corresponds with increased THP in the serum but not in the urine. The overall epithelial polarity of TAL cells does not change, as evidenced by correct apical targeting of Na(+)-K(+)-2Cl cotransporter (NKCC2) and basolateral targeting of Na(+)-K(+)-ATPase. Compared with the wild-type, THP(-/-) mice show a significantly delayed renal recovery after IRI, due possibly to reduced suppression by THP of proinflammatory cytokines and chemokines such as monocyte chemoattractant protein-1 during recovery. Taken together, our data suggest that THP redistribution in the TAL after AKI is a protein-specific event and its increased interstitial presence negatively regulates the evolving inflammatory signaling in neighboring proximal tubules, thereby enhancing kidney recovery. The increase of serum THP may be used as a prognostic biomarker for recovery from AKI.

tuberculosis among Beijing and non-Beijing family strains were not statistically different. The 15-locus set is considered the optimal MIRU-VNTR locus combination for analyzing the M. tuberculosis strains epidemic in this area, while the 10-locus set is an ideal set for first-line molecular typing. We found that the clustering rate of all the M. tuberculosis isolates analyzed was 10.0% using the 15-locus set typing. We conclude that the Beijing family genotype is predominant and that highly epidemic TB and MDR TB are less likely associated with the active transmission of M. tuberculosis in the study area.

Background: The authors compare the effectiveness and safety of endovascular treatment (EVT) versus best medical management (BMM) in strokes attributable to acute basilar artery occlusion (BAO). Methods: The present analysis was based on the ongoing, prospective, multicenter ATTENTION (Endovascular Treatment for Acute Basilar Artery Occlusion) trial registry in China. Our analytic sample comprised 2134 patients recruited at 48 sites between 2017 and 2021 and included 462 patients who received BMM and 1672 patients who received EVT. We performed an inversed probability of treatment weighting analysis. Qualifying patients had to present within 24 hours of estimated BAO. The primary clinical outcome was favorable functional outcome (modified Rankin Scale score, 0–3) at 90 days. We also performed a sensitivity analysis with the propensity score matching–based and the instrumental variable–based analysis. Results: In our primary analysis using the inversed probability of treatment weighting–based analysis, there was a significantly higher rate of favorable outcome at 90 days among EVT patients compared with BMM-treated patients (adjusted relative risk, 1.42 [95% CI, 1.19–1.65]; absolute risk difference, 11.8% [95% CI, 6.9–16.7]). The mortality was significantly lower (adjusted relative risk, 0.78 [95% CI, 0.69–0.88]; absolute risk difference, −10.3% [95% CI, −15.8 to −4.9]) in patients undergoing EVT. Results were generally consistent across the secondary end points. Similar associations were seen in the propensity score matching–based and instrumental variable–based analysis. Conclusions: In this real-world study, EVT was associated with significantly better functional outcomes and survival at 90 days. Well-designed randomized studies comparing EVT with BMM in the acute BAO are needed. Registration: URL: www.chictr.org.cn ; Unique identifier: ChiCTR2000041117.