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Collectively, the present study provides the molecular and functional characterization of POMCDrd2+ neurons and aids our understanding of dopamine-dependent control of homeostatic energy-regulatory neurocircuits.HIV-specific chimeric antigen receptor-T cell (CAR T cell) therapies are candidates to functionally cure HIV infection in people with HIV (PWH) by eliminating reactivated HIV-infected cells derived from latently infected cells within the HIV reservoir. Paramount to translating such therapeutic candidates successfully into the clinic will require anti-HIV CAR T cells to localize to lymphoid tissues in the body and eliminate reactivated HIV-infected cells such as CD4+ T cells and monocytes/macrophages. Here we show that i.v. injected anti-HIV duoCAR T cells, generated using a clinical-grade anti-HIV duoCAR lentiviral vector, localized to the site of active HIV infection in the spleen of humanized mice and eliminated HIV-infected PBMCs. CyTOF analysis of preinfusion duoCAR T cells revealed an early memory phenotype composed predominantly of CCR7+ stem cell-like/central memory T cells (TSCM/TCM) with expression of some effector-like molecules. In addition, we show that anti-HIV duoCAR T cells effectively sense and kill HIV-infected CD4+ T cells and monocytes/macrophages. Furthermore, we demonstrate efficient genetic modification of T cells from PWH on suppressive ART into anti-HIV duoCAR T cells that subsequently kill autologous PBMCs superinfected with HIV. These studies support the safety and efficacy of anti-HIV duoCAR T cell therapy in our presently open phase I/IIa clinical trial (NCT04648046).The HIV latent viral reservoir (LVR) remains a major challenge in the effort to find a cure for HIV. There is interest in lymphocyte-depleting agents, used in solid organ and bone marrow transplantation to reduce the LVR. This study evaluated the LVR and T cell receptor repertoire in HIV-infected kidney transplant recipients using intact proviral DNA assay and T cell receptor sequencing in patients receiving lymphocyte-depleting or lymphocyte-nondepleting immunosuppression induction therapy. CD4+ T cells and intact and defective provirus frequencies decreased following lymphocyte-depleting induction therapy but rebounded to near baseline levels within 1 year after induction. In contrast, these biomarkers were relatively stable over time in the lymphocyte-nondepleting group. The lymphocyte-depleting group had early TCRβ repertoire turnover and newly detected and expanded clones compared with the lymphocyte-nondepleting group. No differences were observed in TCRβ clonality and repertoire richness between groups. These findings suggest that, even with significant decreases in the overall size of the circulating LVR, the reservoir can be reconstituted in a relatively short period of time. These results, while from a relatively unique population, suggest that curative strategies aimed at depleting the HIV LVR will need to achieve specific and durable levels of HIV-infected T cell depletion.Lupus nephritis is a serious complication of systemic lupus erythematosus, mediated by IgG immune complex (IC) deposition in kidneys, with limited treatment options. Kidney macrophages are critical tissue sentinels that express IgG-binding Fcγ receptors (FcγRs), with previous studies identifying prenatally seeded resident macrophages as major IC responders. JPH203 clinical trial Using single-cell transcriptomic and spatial analyses in murine and human lupus nephritis, we sought to understand macrophage heterogeneity and subset-specific contributions in disease. In lupus nephritis, the cell fate trajectories of tissue-resident (TrMac) and monocyte-derived (MoMac) kidney macrophages were perturbed, with disease-associated transcriptional states indicating distinct pathogenic roles for TrMac and MoMac subsets. Lupus nephritis-associated MoMac subsets showed marked induction of FcγR response genes, avidly internalized circulating ICs, and presented IC-opsonized antigen. In contrast, lupus nephritis-associated TrMac subsets demonstrated limited IC uptake, but expressed monocyte chemoattractants, and their depletion attenuated monocyte recruitment to the kidney. TrMacs also produced B cell tissue niche factors, suggesting a role in supporting autoantibody-producing lymphoid aggregates. Extensive similarities were observed with human kidney macrophages, revealing cross-species transcriptional disruption in lupus nephritis. Overall, our study suggests a division of labor in the kidney macrophage response in lupus nephritis, with treatment implications - TrMacs orchestrate leukocyte recruitment while MoMacs take up and present IC antigen.To identify Musashi2 as an effective biomarker regulated by the TGF-β/Smad2/3 signaling pathway for the precise diagnosis and treatment of colorectal cancer (CRC) through bioinformatic tools and experimental verification. The Cancer Genome Atlas, Timer, and Kaplan-Meier analyses were performed to clarify the expression of Musashi2 and its influence on the prognosis of CRC. Transforming growth factor beta 1 (TGF-β1) was used to activate the TGF-β/Smad2/3 signaling pathway to identify whether it could regulate the expression and function of Musashi2. Western blot analysis and quantitative PCR analyses were conducted to verify the expression of Musashi2. Cell counting kit-8 (CCK8), EdU, wound healing, and Transwell assays were conducted to reveal the role of Musashi2 in the proliferation, migration, and invasion of CRC. Musashi2 was upregulated in CRC and promoted proliferation and metastasis. TGF-β1 increased the expression of Musashi2, while the antagonist inducer of type II TGF-β receptor degradation-1 (ITD-1) decreased the expression. CCK8 and EdU assays demonstrated that inhibition of Musashi2 or use of ITD-1 lowered proliferation ability. The Transwell and wound healing assays showed that the migration and invasion abilities of CRC cells could be regulated by Musashi2. The above functions could be enhanced by TGF-β1 by activating the TGF-β/Smad2/3 signaling pathway and reversed by ITD-1. A positive correlation was found between Musashi2 and the TGF-β/Smad2/3 signaling pathway. TGF-β1 activates the TGF-β/Smad2/3 pathway to stimulate the expression of Musashi2, which promotes the progression of CRC. Musashi2 might become a target gene for the development of new antitumor drugs.Based on the selective ClO--triggered chlorination reaction and the subsequent pKa decrease of phenols, a new strategy was developed for rationally designing ratiometric ClO- fluorescent probes with high selectivity. By investigating the fluorescence responses of 6-cyano-2-naphthol toward ClO- and the pKa-dependent response mechanism, we developed a rapid, sensitive and selective two-photon ratiometric fluorescent probe, Naph-DFOB, to detect ClO-. This probe displayed a ratiometric fluorescence change (from 509 nm to 628 nm) toward ClO- and was successfully applied to image intracellular ClO- in living cells with two-photon excitation. Using Naph-DFOB as a useful tool, the investigation of lipopolysaccharide (LPS)-induced acute lung injury in a mouse model was effectively performed.A family of amphiphilic diblock copolymers containing a hydrophobic polyisobutylene (PIB, Mn = 1000 g mol-1) segment and a hydrophilic block with sugar pendants has been synthesized by combining living cationic and reversible addition-fragmentation chain transfer (RAFT) polymerization techniques; to explore their potential in insulin fibrillation inhibition. The glucose content in the hydrophilic segment has been tailor-made from 20 to 57 units to prepare block copolymers. The removal of the acetates from the pendent glucose units resulted in amphiphilic block copolymers that generated micellar aggregates in aqueous media. The treatment of insulin with these block copolymers affected the fibril formation process which was demonstrated using an array of biophysical techniques, namely, thioflavin T (ThT) fluorescence, tyrosine (Tyr) fluorescence, Nile red (NR) fluorescence, isothermal titration calorimetry (ITC), etc. The Tyr fluorescence assay and NR fluorescence study revealed the crucial role of hydrophobic interaction in the inhibition process, whereas ITC measurements confirmed the importance of polar interaction. Thus, the block copolymers exhibit potent inhibition of insulin fibrillation owing to hydrophobic (from PIB segment) and glycosidic cluster effect (from sugar pendant block).Molecular diagnostics has expanded to become the standard of care for a variety of solid tumor types. With limited diagnostic material, it is often desirable to use cytological preparations to provide rapid and accurate molecular results. This review covers important pre-analytic considerations and limitations, and a description of common techniques that the modern cytopathologist should understand when ordering and interpreting molecular tests in practice.Background Research suggests construction industry workers (CIWs) face increased suicide vulnerability. Aims The current study synthesizes international evidence examining rates, risk, and drivers of CIW suicide. Method Comprehensive searches of MEDLINE, PsycInfo, Embase, Emcare, Web of Science, Scopus, and gray literature were undertaken, identifying studies that discussed, theorized about, or demonstrated risks and/or rates and/or drivers of CIW suicide, without inclusion of other industries. Results A number of included studies statistically analyzed suicide outcomes in a variety of CIW populations, with the majority reporting increased rate and/or risk, however significant heterogeneity limited comparisons. Twenty-five potential drivers were identified and classified as personal- or industry-related. Disentanglement highlighted the relevance of previously understood personal drivers, need for future focus on industry drivers, and potential interplay between drivers. Limitations Exclusion of non-English articles as well as inability to extend analysis to fully understand rates and/or risk of CIW suicide and tenuous links between suggested drivers and suicide outcomes. Conclusion Despite limitations, this paper aids understanding in relation to the suggestion that CIWs are at increased suicide vulnerability. Disentanglement of potential drivers demonstrates the importance of future research focused on industry drivers to assist in prevention strategies.Segmental overgrowth syndromes include a group of clinical entities, all characterized by the abundant proliferation of tissues or organs in association with vascular abnormalities. These syndromes show a wide spectrum of severity ranging from limited involvement of only small areas of the body to complex cases with impressive distortions of multiple tissues and organs. It is now clear that somatic mutations in genes of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway (in brief "mTOR pathway") are responsible for such entities. Not all the cells of the body carry the same causative mutation, which is mosaic, appearing from two (or more) distinct cell lineages after fertilization. In this article, we reconsider the clinical spectrum and surveillance programs of patients with segmental overgrowth syndromes, based on the features of six patients with diverse clinical forms of overgrowth and pathogenic variants in genes of the mTOR pathway.