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Muscle wasting is the key manifestation of cancer-associated cachexia, a lethal metabolic disorder seen in over 50% of cancer patients. Autophagy is activated in cachectic muscle of cancer hosts along with the ubiquitin-proteasome pathway (UPP), contributing to accelerated protein degradation and muscle wasting. However, established signaling mechanism that activates autophagy in response to fasting or denervation does not seem to mediate cancer-provoked autophagy in skeletal myocytes. Here, we show that p38β MAPK mediates autophagy activation in cachectic muscle of tumor-bearing mice via novel mechanisms. Complementary genetic and pharmacological manipulations reveal that activation of p38β MAPK, but not p38α MAPK, is necessary and sufficient for Lewis lung carcinoma (LLC)-induced autophagy activation in skeletal muscle cells. Particularly, muscle-specific knockout of p38β MAPK abrogates LLC tumor-induced activation of autophagy and UPP, sparing tumor-bearing mice from muscle wasting. Mechanistically, p38β MAPK-mediated activation of transcription factor C/EBPβ is required for LLC-induced autophagy activation, and upregulation of autophagy-related genes LC3b and Gabarapl1. Surprisingly, ULK1 activation (phosphorylation at S555) by cancer requires p38β MAPK, rather than AMPK. Activated ULK1 forms a complex with p38β MAPK in myocytes, which is markedly increased by a tumor burden. Overexpression of a constitutively active p38Tbeta; MAPK in HEK293 cells increases phosphorylation at S555 and other amino acid residues of ULK1, but not several of AMPK-mediated sites. Finally, ULK1 activation is abrogated in tumor-bearing mice with muscle-specific knockout of p38β MAPK. Thus, p38β MAPK appears a key mediator of cancer-provoked autophagy activation, and a therapeutic target of cancer-induced muscle wasting.

Atomically precise metal clusters are attractive as highly efficient catalysts, but suffer from continuous efficiency deactivation in the catalytic process. Here, we report the development of an efficient strategy that enhances catalytic performance by electropolymerization (EP) of metal clusters into hybrid materials. Based on carbazole ligand protection, three polymerized metal-cluster hybrid materials, namely Poly-Cu 14 cba, Poly-Cu 6 Au 6 cbz and Poly-Cu 6 Ag 4 cbz, were prepared. Compared with isolated metal clusters, metal clusters immobilizing on a biscarbazole network after EP significantly improved their electron-transfer ability and longterm recyclability, resulting in higher catalytic performance. As a proof-of-concept, Poly-Cu 14 cba was evaluated as an electrocatalyst for reducing nitrate (NO 3 À ) to ammonia (NH 3 ), which exhibited � 4-fold NH 3 yield rate and � 2-fold Faraday efficiency enhancement compared to that of Cu 14 cba with good durability. Similarly, Poly-Cu 6 Au 6 cbz showed 10 times higher photocatalytic efficiency towards chemical warfare simulants degradation than the cluster counterpart.

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Bullous pemphigoid (BP) is the most common subepidermal autoimmune blistering disease. It usually affects people older than 70 years of age. The two main autoantigens are BP180 and BP230, both of which are components of hemidesmosomes. Immunoglobulin (Ig)G and IgE autoantibodies to BP180 detected by the enzyme-linked immunoassay (ELISA) show close associations with the activity and severity of BP. In addition, inflammatory cells (eosinophils, neutrophils and mast cells) and cytokines (e.g. interleukins and CC chemokine ligands) play an important part in the pathogenesis, activity and severity of BP. We summarized the potential contribution of each factor postulated to be associated with the activity and severity of BP, and provide guidance for clinicians to pay timely and close attention to such parameters. This review may also promote the development of novel therapies for BP. KEY MESSAGES Bullous Pemphigoid Disease Area Index (BPDAI) is a scoring system which can reflect the extent of clinical involvement of BP patients. The titres of IgE autoantibodies and IgG autoantibodies against the NC16A domain of BP180 are closely correlated with the activity and severity of BP. Many inflammatory cells and molecules, such as eosinophils and interleukins, can also reflect the activity and severity of BP.

Background Health-related quality of life (HRQOL) is becoming an increasingly important outcome in kidney transplantation. To describe HRQOL in kidney transplant recipients (KTRs), this systematic review summarizes literature that compared HRQOL between KTRs to other relevant populations (i.e. patients receiving dialysis, patients on the waiting list for kidney transplantation, patients with chronic kidney disease [CKD] not receiving renal replacement therapy (RRT), the general population, and healthy controls) and themselves before kidney transplantation. Methods The literature search was conducted in PubMed, EMBASE, Web of Science, and COCHRANE Library. Eligible studies published between January 2000 and October 2020 were included. Results 44 studies comprising 6929 KTRs were included in this systematic review. Despite the study heterogeneity, KTRs reported a higher HRQOL after kidney transplantation compared with pre-transplantation and compared with patients receiving dialysis with or without being on the waiting list, especially in disease-specific domains (i.e. burden and effects of kidney disease). Additionally, KTRs had similar to marginally higher HRQOL compared with patients with CKD stage 3-5 not receiving RRT. When compared with healthy controls or the general population, KTRs reported similar HRQOL in the first one or two years after kidney transplantation, and lower physical HRQOL and lower to comparable mental HRQOL in studies with longer post-transplant time. Conclusions The available evidence suggests that HRQOL improves after kidney transplantation and can be restored to but not always maintained at pre-CKD HRQOL levels. Future studies investigating intervention targets to improve or maintain post-transplant HRQOL are needed.

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