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PtII based organometallic photosensitizers (PSs) have emerged as novel potent photodynamic inactivation (PDI) reagents through their enhanced intersystem crossing (ISC) processes. Currently, few PtII PSs have been investigated as antibacterial materials, with relatively poor performances reported and with structure‐activity relationships not well described. Herein, a pair of configurational isomers are reported of Bis‐BODIPY (4,4‐difluoro‐boradizaindacene) embedded PtII PSs. The cis‐isomer (cis‐BBP) displayed enhanced 1O2 generation and better bacterial membrane anchoring capability as compared to the trans‐isomer (trans‐BBP). The effective PDI concentrations (efficiency > 99.9%) for cis‐BBP in Acinetobacter baumannii (multi‐drug resistant (MDR)) and Staphylococcus aureus are 400 nM (12 J cm−2) and 100 nM (18 J cm−2), respectively; corresponding concentrations and light doses for trans‐BBP in the two bacteria are 2.50 µM (30 J cm−2) and 1.50 µM (18 J cm−2), respectively. The 50% and 90% minimum inhibitory concentration (MIC50 and MIC90) ratio of trans‐BBP to cis‐BBP is 22.22 and 24.02 in A. baumannii (MDR); 21.29 and 22.36 in methicillin resistant S. aureus (MRSA), respectively. Furthermore, cis‐BBP displays superior in vivo antibacterial performance, with acceptable dark and photoinduced cytotoxicity. These results demonstrate cis‐BBP is a robust light‐assisted antibacterial reagent at sub‐micromolecular concentrations. More importantly, configuration of PtII PSs should be an important issue to be considered in further PDI reagents design. [ABSTRACT FROM AUTHOR]

Locus coeruleus (LC) dysfunction is involved in the pathophysiology of depression; however, the neural circuits and specific molecular mechanisms responsible for this dysfunction remain unclear. Here, it is shown that activation of tyrosine hydroxylase (TH) neurons in the LC alleviates depression‐like behaviors in susceptible mice. The dorsolateral septum (dLS) is the most physiologically relevant output from the LC under stress. Stimulation of the LCTH‐dLSSST innervation with optogenetic and chemogenetic tools bidirectionally can regulate depression‐like behaviors in both male and female mice. Mechanistically, it is found that brain‐derived neurotrophic factor (BDNF), but not norepinephrine, is required for the circuit to produce antidepressant‐like effects. Genetic overexpression of BDNF in the circuit or supplementation with BDNF protein in the dLS is sufficient to produce antidepressant‐like effects. Furthermore, viral knockdown of BDNF in this circuit abolishes the antidepressant‐like effect of ketamine, but not fluoxetine. Collectively, these findings underscore the notable antidepressant‐like role of the LCTH‐dLSSST pathway in depression via BDNF‐TrkB signaling. [ABSTRACT FROM AUTHOR]