The chromatin remodeling complex SWI/SNF is highly conserved and plays critical roles in various cellular processes including transcription and DNA damage repair 1 , 2 . It hydrolyzes ATP to remodel chromatin structure by sliding and evicting histone octamers 3 - 8 , creating DNA regions that become accessible to other essential factors. However, our mechanistic understanding of the remodeling activity is largely hindered by the lack of a high-resolution structure of any complex from this family. Here we report the first structure of SWI/SNF from the yeast S. cerevisiae bound to a nucleosome at near atomic resolution determined by cryo-electron microscopy (cryo-EM). In the structure, the Arp module is sandwiched between the ATPase and the rest of the complex, with the Snf2 HSA domain connecting all modules. The body contains an assembly scaffold composed of conserved subunits Snf12 (SMARCD/BAF60), Snf5 (SMARCB1/BAF47/ INI1) and an asymmetric dimer of Swi3 (SMARCC/BAF155/170). Another conserved subunit Swi1 (ARID1/BAF250) resides in the core of SWI/SNF, acting as a molecular hub. We also observed interactions between Snf5 and the histones at the acidic patch, which could serve as an anchor during active DNA translocation. Our structure allows us to map and rationalize a subset of cancer-related mutations in the human SWI/SNF complex and propose a model of how SWI/SNF recognizes and remodels the +1 nucleosome to generate nucleosome-depleted regions during gene activation 9 .

ObjectiveThe protein post-translational modification (PTM) in host cells can be rewritten by bacterial enzymes and represents an unprecedented mechanism in the communication between intestinal flora and the host. AlthoughAkkermansia muciniphilahas been widely investigated as a probiotic and blunts colitis-associated tumourigenesis in mice, there is little understanding regarding whetherA. muciniphilais involved in the PTM of colorectal cancer (CRC). This study investigates whether and howA. muciniphilaengages in the PTM of host CRC.DesignThe secreting extracellular vesicles fromA. muciniphilaand purified Amuc_2172 were used for different tumourigenesis mice models. Amuc_2172-induced immune activity of CD8+cytotoxic T lymphocytes (CTLs) were evaluated in vitro and in vivo. The acetyltransferase activity and downstream target genes of Amuc_2172 were investigated.ResultsAmuc_2172, a general control non-derepressible 5-related acetyltransferase ofA. muciniphila, was accessible to colorectal cells by macropinocytosis and functioned as an acetyltransferase of Lys14 on histone H3 (H3K14ac). Elevated H3K14ac onHspa1aloci promoted the transcription and secretion of heat-shock protein 70 (HSP70) in cancer cells. High level of HSP70 promoted the immune activity of CTLs in vitro and in vivo. Moreover, bioengineered nanoparticles provided a safe and reliable drug delivery strategy of Amuc_2172 for CRC treatment in an allograft mice model.ConclusionAmuc_2172 reprogrammed tumour microenvironment by inducing HSP70 secretion and promoting CTL-related immune response in the process of tumourigenesis.

Thalidomide was initially developed as a sedative; subsequently, its use was expanded to treat morning sickness in pregnant women. However, it was later discovered to be a teratogenic drug that was associated with embryopathy in women. A woman is described who was exposed to thalidomide in utero. She had several stigmata of thalidomide embryopathy. Although treatment of nausea and anxiety in pregnant women with thalidomide was discontinued in 1961, the drug has been found to be a useful agent for the management of several systemic conditions and dermatological disorders. Whether the treatment with thalidomide shall be incorporated in the therapeutic regime for patients with severe coronavirus disease 2019 (COVID-19) infection remains to be determined.

Vitiligo is a skin condition that causes loss of pigmentation, resulting in hypopigmented and depigmented patches on the skin. Vitiligo has been associated with many autoimmune conditions. A 27-year-old female with a history of vitiligo had a clinical presentation and laboratory studies that were consistent with incipient hypothyroidism. The relationship between vitiligo, hypothyroidism, and other autoimmune conditions is discussed.

Bupropion is an oral antidepressant that is commonly used to treat various mood disorders. Its therapeutic mechanism of action results from inhibiting the reuptake of norepinephrine and dopamine. Bupropion is generally well-tolerated and patients usually experience no side effects or mild adverse events. Rarely, hypersensitivity reactions to bupropion, such as urticaria, have been observed. However, the prevalence of delayed onset bupropion-associated urticaria may not be properly reflected in the literature due to misdiagnosis of the condition caused by its atypical presentation. We report a 20-year-old man with delayed onset bupropion-associated urticaria; he had been on bupropion for three weeks and subsequently developed new severely pruritic, erythematous wheals on his abdomen, bilateral flanks, and upper extremities. The clinical features of this rare adverse reaction to bupropion are also summarized.

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