Designing effective and selective reactions at sustainable or mild conditions is key for the valorization or refinery of lignin biomass using H2 reduction methods. However, it remains unclear what are the feasible mildest conditions for the reductive valorization of lignin, at which transformations can be designed. Here, we aim to exploit this critically important question using quantum chemistry calculations to systematically analyze the thermodynamics of hydrogenation and hydrogenolysis of typical functional groups found in lignin based on a set of aromatic model compounds. Our results show that it is thermodynamically feasible to break ether linkages and remove oxygen content in the model compounds even at room temperature, room pressure, and in aqueous solvent (i.e., the global mildest conditions). Interestingly, the potential influence on the thermodynamics by reaction variables is ranked in the order of temperature > H2 pressure > solvent dielectric constant; a strategically chosen solvent may enable increased selectivity for hydrogenolysis over hydrogenation. Our predicted reaction thermodynamics is consistent with our experimental findings of probed reaction pathways. This work may inspire researchers to pursue the design of “ultimate” green biomass conversion processes closer to the global mildest conditions.

Rationale:We hope to increase awareness that hypokalemic paralysis may be the first presentation of Sjögren syndrome, for which potassium-sparing diuretics can be an effective adjunct to potassium replenishment.Presenting concerns:A 73-year-old female presented to a peripheral hospital with quadriparesis and a critically low serum potassium of 1.6 mmol/L with U waves on the electrocardiogram (ECG). The initial arterial blood gas showed a pH of 7.19, bicarbonate of 13 mEq/L, and a CO2 of 35 mm Hg. Over the next 6 days, she was administered a total of 450 mEq of potassium supplements. Despite this, her potassium never increased above 2.9 mmol/L and was thus transferred to the University Hospital for further management. On arrival, her vital signs were within normal limits. Her only other symptoms were fatigue and ocular dryness. Physical exam showed slightly weakened quadriceps muscles bilaterally, graded 4/5. Examination was otherwise unremarkable. Admission investigations included a potassium of 2.8 mmol/L, chloride 118 mmol/L, sodium 136 mmol/L, and eGFR 48 mL/min/1.73 m2. Renin aldosterone ratio was normal.Diagnoses:Distal renal tubular acidosis (RTA) was diagnosed based on a normal anion gap metabolic acidosis, positive urine anion gap, and elevated urine potassium to creatinine ratio. Investigation of underlying causes revealed a positive Antinuclear antibody (ANA), elevated rheumatoid factor, and high anti-Ro/SSA titre which directed us toward a unifying diagnosis of Sjögren syndrome. A renal biopsy was undertaken as an outpatient and demonstrated severe interstitial nephritis with acute and chronic components, parenchymal scarring, atrophy, and small vessel arteriosclerosis.Interventions:In the acute setting, the patient was treated with bicarbonate and amiloride in addition to potassium supplementation.Outcomes:The patient’s hypokalemic paralysis and metabolic acidosis were corrected.Lessons Learned:Severe hypokalemic paralysis in distal RTA associated with Sjögren syndrome can be successfully treated with amiloride in addition to potassium supplementation. We also review the literature on the aberrancies seen in H+ATPase, Band 3, Pendrin, and carbonic anhydrase that may underlie the pathogenesis of distal RTA in Sjögren syndrome.

Herein, an efficient, scalable, and concise approach to an advanced pyrroloiminoquinone synthetic intermediate (6b) by way of a Larock indole synthesis is reported. The synthetic utility of this intermediate is demonstrated by its ready conversion to makaluvamines A (1) and K (4).

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RELA haploinsufficiency is a recently described autoinflammatory condition presenting with intermittent fevers and mucocutaneous ulcerations. The RELA gene encodes the p65 protein, one of five NF-κB family transcription factors. As RELA is an essential regulator of mucosal homeostasis, haploinsufficiency leads to decreased NF-κB signaling which promotes TNF-driven mucosal apoptosis with impaired epithelial recovery. Thus far, only eight cases have been reported in the literature. Here, we report four families with three novel and one previously described pathogenic variant in RELA. These four families included 23 affected individuals for which genetic testing was available in 16. Almost half of these patients had been previously diagnosed with more common rheumatologic entities (such as Behcet’s Disease; BD) prior to the discovery of their pathogenic RELA variants. The most common clinical features were orogenital ulcers, rash, joint inflammation, and fever. The least common were conjunctivitis and recurrent infections. Clinical variability was remarkable even among familial cases, and incomplete penetrance was observed. Patients in our series were treated with a variety of medications, and benefit was observed with glucocorticoids, colchicine, and TNF inhibitors. Altogether, our work adds to the current literature and doubles the number of reported cases with RELA-Associated Inflammatory Disease (RAID). It reaffirms the central importance of the NF-κB pathway in immunity and inflammation, as well as the important regulatory role of RELA in mucosal homeostasis. RELA associated inflammatory disease should be considered in all patients with BD, particularly those with early onset and/or with a strong family history.