Metabolic regulator LKB1 controls adipose tissue ILC2 PD-1 expression and mitochondrial homeostasis to prevent insulin resistance.

Adipose tissue group 2 innate lymphoid cells (ILC2s) help maintain metabolic homeostasis by sustaining type 2 immunity and promoting adipose beiging. Although impairment of the ILC2 compartment contributes to obesity-associated insulin resistance, the underlying mechanisms have not been elucidated. Here, we found that ILC2s in obese mice and humans exhibited impaired liver kinase B1 (LKB1) activation. Genetic ablation of LKB1 disrupted ILC2 mitochondrial metabolism and suppressed ILC2 responses, resulting in exacerbated insulin resistance. Mechanistically, LKB1 deficiency induced aberrant PD-1 expression through activation of NFAT, which in turn enhanced mitophagy by suppressing Bcl-xL expression. Blockade of PD-1 restored the normal functions of ILC2s and reversed obesity-induced insulin resistance in mice. Collectively, these data present the LKB1-PD-1 axis as a promising therapeutic target for the treatment of metabolic disease.

LKB1 prevents ILC2 exhaustion to enhance antitumor immunity.

Group 2 innate lymphoid cells (ILC2s) play crucial roles in mediating allergic inflammation. Recent studies also indicate their involvement in regulating tumor immunity. The tumor suppressor liver kinase B1 (LKB1) inactivating mutations are associated with a variety of human cancers; however, the role of LKB1 in ILC2 function and ILC2-mediated tumor immunity remains unknown. Here, we show that ablation of LKB1 in ILC2s results in an exhausted-like phenotype, which promotes the development of lung melanoma metastasis. Mechanistically, LKB1 deficiency leads to a marked increase in the expression of programmed cell death protein-1 (PD-1) in ILC2s through the activation of the nuclear factor of activated T cell pathway. Blockade of PD-1 can restore the effector functions of LKB1-deficient ILC2s, leading to enhanced antitumor immune responses in vivo. Together, our results reveal that LKB1 acts to restrain the exhausted state of ILC2 to maintain immune homeostasis and antitumor immunity.

PLZF restricts intestinal ILC3 function in gut defense.

Group 3 innate lymphoid cells (ILC3s) play important roles in maintaining intestinal homeostasis by protecting the host from pathogen infections and tissue inflammation. The transcription factor PLZF (promyelocytic leukemia zinc finger), encoded by zinc finger BTB domain containing 16 (Zbtb16), is highly and transiently expressed in ILC precursors (ILCPs). However, the role of PLZF in regulating ILC3 development and function remains unknown. Here, we show that PLZF was specifically expressed in mature intestinal ILC3s compared with other ILC subsets. PLZF was dispensable for ILC3 development. However, PLZF deficiency in ILC3s resulted in increased innate interleukin-22 (IL-22) secretion and protection against gut infection and inflammation. Mechanistically, PLZF negatively regulated IL-22 expression by ILC3s in a cell-intrinsic manner by binding to the IL-22 promoter region for transcriptional repression. Together, our data suggest that PLZF restricts intestinal ILC3 function to regulate gut immune homeostasis.

Construction of metal-organic framework/polymer beads for efficient lead ions removal from water: Experiment studies and full-scale performance prediction.

Metal-organic frameworks (MOFs) show great promise in heavy metal removal; however, their applications are restricted by the poor separability and water instability. Herein, granular Zr-based MOF-polymer composite beads (MPCB(Zr)) (mean diameter âˆ¼ 1.74 mm) were synthesized using a facile dropping method, and applied on efficient lead ions (Pb(II)) removal. The as-prepared MPCB(Zr) demonstrated deep Pb(II) removal capability by reducing its concentration to âˆ¼ 0.002 mg L-1 after adsorption equilibrium at 360 min. The distribution coefficient for Pb(II) reached 8.0 × 106 mL g-1, and the theoretical adsorption capacity for Pb(II) was 144.5 mg g-1 (0.70 mmol g-1, 30 °C). The resulting MPCB(Zr) was highly selective for Pb(II), with the selectivity coefficient up to âˆ¼ 1.0-3.6 × 103 for the background cations (Na(I), K(I), Ca(II), and Mg(II)). Moreover, the MPCB(Zr) exhibited a broad working pH range (3.0-6.0) and satisfactory anti-interference to dissolved organic matters (humic acid and fuvic acid). Notably, the MPCB(Zr) also demonstrated excellent reusability with the Pb(II) removal efficiency over 99.0% after 20 cycles. Combined physicochemical characterizations unveiled that the thiol and oxygen-containing groups (e.g., hydroxyl, carboxylate) were responsible for the effective Pb(II) removal. To provide guidance for engineering application, the full-scale performance of the MPCB(Zr) under varying operation conditions was systematically evaluated via the validated pore surface diffusion model. This work provides an effective methodology to construct macroscopic MOF-polymer beads for effective Pb(II) removal, and promote the actual application of MOFs in water treatment.

Preparation of Tea Aroma Precursor Glycosides: An Efficient and Sustainable Approach via Chemical Glycosidation.

Tea aroma precursor glycosides are plant-derived natural products with great economic value. However, the preparation of these glycosides remains largely overlooked in the past decades. Herein, we report a mild, efficient, and sustainable chemocatalytic procedure for the production of tea aroma precursor glycosides. During the study of the glycosidation, the catalysts were found to be decisive in the product formation favoring different reaction pathways; in addition, the influence of molecular sieves was elucidated. With regard to these findings, the serious problem of the competing orthoester formation side reaction was successfully overcome with low catalyst loading (1 mol %) and the use of 5 Å molecular sieves, leading to the preparation of a variety of tea aroma precursor ß-d-glucopyranosides and ß-primeverosides on a gram scale in high yields in an economical way. Taken together, the current approach features catalytic glycosidation with non-toxic and low-cost catalysts, demonstrates highly favorable greenness and sustainability, and promises industrial production of tea aroma precursor glycosides.

Plasma heat shock protein 90alpha as a biomarker for the diagnosis of liver cancer: in patients with different clinicopathologic characteristics.

PURPOSES: The purposes of this study were to assess the correlation between the plasma level of Hsp90α and the clinicopathological characteristics of patients with liver cancer and compare the diagnostic efficacy of Hsp90α, AFP, CEA, and CA199 in HCC. EXPERIMENTAL DESIGN: A total of 200 individuals, including 140 patients with liver cancer or benign liver diseases and 60 healthy people, were enrolled for quantitative measurement of plasma Hsp90α by ELISA. RESULTS: The plasma level of Hsp90α was significantly different between patients with liver cancer or benign liver diseases and healthy controls (P < 0.001). The sensitivity, specificity, and AUC (95% CI) of Hsp90α were 93.2%, 85.4%, and 0.931% (0.891-0.972%), respectively, when Hsp90α was applied to differentiate liver cancer patients and healthy controls. Significant positive correlations between the plasma Hsp90α level and clinicopathological characteristics such as the history of basic liver disease (P = 0.038), active stage of hepatitis (P = 0.039), Child-Pugh score (P < 0.001), size of focal liver lesions (P = 0.004), and extrahepatic metastasis (P < 0.001) were observed. AFP + Hsp90α was the best combination strategy for the auxiliary diagnosis of HCC, with a sensitivity of 95.7%, a specificity of 97.5%, and an AUC of 0.990 (0.976-1.000). The level of plasma Hsp90α decreased significantly (P < 0.001) after resection of tumor tissue. CONCLUSIONS: This study demonstrated that plasma Hsp90α levels are useful as a diagnostic biomarker in liver cancer and may predict the responses of patients with liver cancer to surgery. Some clinicopathological characteristics could affect the plasma Hsp90α levels.

Leishmania lipophosphoglycan components: A potent target for synthetic neoglycoproteins as a vaccine candidate for leishmaniasis.

Leishmania is an obligate intracellular pathogen that invades phagocytic host cells. Due to its high morbidity and mortality rates, leishmaniasis attracts significant attention. The disease, which is caused by Leishmania parasites, is distributed worldwide, particularly among developing communities, and causes fatal complications if not treated expediently. Unfortunately, the existing treatments are not preventive and do not impede Leishmania infection. Many drugs available for leishmaniasis are becoming less effective due to emerging resistance in some Leishmania species. Other drugs have drawbacks such as low cost-effectiveness, toxicity, and side effects. The World Health Organization (WHO) considers leishmaniasis to be a major public health problem and suggests that the best prevention is to develop a vaccine for this dangerous disease. In this review, we focus on the unique components of lipophosphoglycan (LPG), a component of the Leishmania cell wall, particularly [Galp(1 → 4)-ß-[Manp-(1 → 2)-α-Manp-(1 → 2)-α]-Manp] in the cryptic tetrasaccharide cap, and on synthetic approaches as a potent candidate for a leishmaniasis vaccine.

Single-incision or conventional laparoscopic adjustable gastric banding: A systematic review.

INTRODUCTION: Single-incision laparoscopic surgery (SILS) in gastric banding (SI-LAGB) has been reported to be a safe and technically feasible procedure among various operating methods. However, there is little evidence with regard to the question whether SI-LAGB has more advantages and should be recommended compared with conventional LAGB (CLAGB). Thus, this study was performed to assess the safety and efficacy of SI-LAGB. MATERIAL AND METHODS: A computerized search of the electronic databases PubMed and EMBASE was performed. Data regarding operative parameters, postoperative recovery parameters, follow-up time, percentage of excess weight loss, and postoperative complication were pooled and analyzed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. RESULTS: Ten comparative studies including 2,073 patients (1,038 patients who received SI-LAGB and 1,035 patients who received CLAGB) were included and analyzed. Compared with CLAGB, a similar weight loss could be obtained using SI-LAGB. The postoperative complications of SI-LAGB were within the acceptable range, but one study reported one perioperative death. SI-LAGB required a longer operative time. Other outcome variables, such as blood loss, days of hospitalization, pain score, and hospitalization costs, were not significantly different between the two groups. CONCLUSIONS: SI-LAGB might be a safe and effective alternative to C-LAGB when performed by experienced surgeons, but available data do not allow to give a definitive answer and randomized controlled trials are needed.