Cage-confined photocatalysis for wide-scope unusually selective [2 + 2] cycloaddition through visible-light triplet sensitization.

Light-induced [2 + 2] cycloaddition is the most straightforward way to generate cyclobutanes, which are core structures of many natural products, drugs and bioactive compounds. Despite continuous advances in selective [2 + 2] cycloaddition research, general method for intermolecular photocatalysis of acyclic olefins with specific regio- and diastereoselectivity, for example, syn-head-to-head (syn-HH) cyclobutane derivatives, is still lack of development but highly desired. Herein, we report a cage-confined photocatalytic protocol to enable unusual intermolecular [2 + 2] cycloaddition for α,ß-unsaturated carbonyl compounds. The syn-HH diastereomers are readily generated with diastereoselectivity up to 99%. The cage-catalyst is highly efficient and robust, covering a diverse substrate range with excellent substituent tolerance. The mimic-enzyme catalysis is proposed through a host-guest mediated procedure expedited by aqueous phase transition of reactant and product, where the supramolecular cage effect plays an important role to facilitate substrates inclusion and pre-orientation, offering a promising avenue for general and eco-friendly cycloaddition photocatalysis with special diastereoselectivity.

Comparison of bipolar hemiarthroplasty and total hip arthroplasty for displaced femoral neck fractures in the healthy elderly: a meta-analysis.

BACKGROUND: Displaced femoral neck fractures (FNFs) in healthy elderly patients have traditionally been managed with hemiarthroplasty (HA) or total hip arthroplasty (THA), with studies suggesting that THA may be the better option. However, it has recently been reported that bipolar HA (BHA) also provides good outcomes, and it is not clear as to whether BHA or THA is most appropriate. The purpose of this study was to conduct a meta-analysis of randomized controlled trials (RCTs) comparing the outcomes of BHA with THA for treating FNF in healthy elderly patients. METHODS: We searched the following databases from inception to May 2015 for relevant RCTs without language restrictions: PubMed, the Cochrane Central Register of Controlled Trials, Ovid MEDLINE and EMBASE, CINAHL, the China Biological Medicine Database, International Clinical Trials Registry Platform, Current Controlled Trials, and ClinicalTrials.gov. RCTs that met the inclusion criteria were statistically analyzed using the Cochrane review methods. RESULTS: Eight RCTs were included (total 1,014 patients; 523 had BHA and 491 had THA). The data from included RCTs were divided into four subgroups according to different follow-up durations. The Harris Hip Score after BHA was not different from that after THA in all subgroups. Both reoperation rate and acetabular erosion rate were higher after BHA after more than 4 years, while there was a higher dislocation rate associated with THA within 4 years. THA was more favorable regarding the EQindex-5D and the mobility and pain rate, while BHA was more favorable regarding operating time. No significant differences were found regarding infection rate, general complications, 1-year mortality, blood loss, and length of postoperative hospital stay. CONCLUSIONS: For healthy elderly patients with displaced FNFs, treatment with BHA led to better outcomes regarding dislocation rate, while THA was better regarding acetabular erosion rate and reoperation rate. When comparing BHA with THA, there were no significant differences in other important outcomes such as Harris Hip Score, infection rate, general complications, and 1-year mortality. Further high-quality RCTs are needed to provide robust evidence and evaluate the treatment options.

CD4+ T cells initiate pancreatic islet xenograft rejection via an interferon-gamma-dependent recruitment of macrophages and natural killer cells.

BACKGROUND: In this study, the mechanisms by which CD4+ T cells interact with the innate immune system in xenograft rejection were investigated. METHODS: Fetal pig pancreas (FPP) grafts were transplanted into female SCID mice. The FPP recipient SCID mice were reconstituted with exogenous leukocytes obtained from male BALB/c mice. RESULTS: Although nonreconstituted SCID recipients or recipients reconstituted with CD4+ T cell-depleted leukocytes showed indefinite FPP graft survival with very few macrophages infiltrating their grafts, reconstitution of SCID recipients with as few as 2x10(5) CD4+ T cells was sufficient to induce rapid xenograft rejection. CD4+ T cells secreted interferon-gamma but not interleukin-4 and initiated the activation and accumulation of macrophages and natural killer cells, that were responsible for the rapid graft destruction. Suppression of interferon-gamma prolonged graft survival and suppressed the macrophages and natural killer cell accumulation and activation. CONCLUSIONS: These results demonstrate that CD4+ T cell-dependent cellular xenograft rejection was a result of macrophage and natural killer cell accumulation and activation, but was not mediated by eosinophils. Consistent with this was the finding that interferon-gamma but not interleukin-4 was in part responsible for mediating this effect.

Transfection of tubule cells with Fas ligand causes leukocyte apoptosis.

BACKGROUND: Since the Fas/Fas Ligand (FasL) interaction is recognized as a major pathway of apoptosis in immune cells, we hypothesized that selective expression of FasL by tubular cells (TC) may promote the resolution of interstitial inflammation by inducing apoptosis of infiltrating immune cells. In this study, the effect of FasL transfection of rat TC on apoptosis of leukocytes was examined. METHODS: Rat tubule cells (NRK52E) were transfected with plasmids constructed using human and rat FasL (hFasL and rFasL). The propensity of activated, transfected TC to undergo apoptosis was examined. Similarly, the effects of FasL transfection on apoptosis of Jurkat cells and activated leukocytes were assessed directly following co-culture for 12 hours and in a cell insert system intended to assess the effects of soluble FasL. Fas and FasL expression was assessed by flow cytometry and apoptosis was examined using Annexin V staining and the TUNEL method. RESULTS: Expression of FasL in TC was increased after FasL transfection. Transfected TC showed no detectable increase in apoptosis following lipopolysaccharide (LPS) or tumor necrosis factor-alpha (TNF-alpha) activation. Jurkat cell apoptosis was increased ninefold and eightfold after co-culture with TC transfected with hFasL and rFasL, respectively (67.0 +/- 12.1% and 60.1 +/- 8.8% vs. 6.7 +/- 1.8% with un-transfected TC, P < 0.01). Similarly, apoptosis of activated leukocytes was increased fourfold by co-culture (26.8 +/- 4.9% vs. 6.7 +/- 2.0% with untransfected TC, P < 0.01). Leukocyte apoptosis also was increased in an insert culture system (18.2 +/- 4.4% vs. 5.8 +/- 2.3% with un- transfected TC, P < 0.01). No increase of TC apoptosis was detected in any of the co-culture experiments. CONCLUSION: Enhanced expression of FasL by TC is capable of inducing apoptosis of activated leukocytes, without evidence for increased susceptibility to apoptosis of the transfected cells themselves. This suggests a potential role for this approach in the limitation and resolution of renal tubulointerstitial inflammation.