The Taybi-Linder syndrome (TALS) is a rare genetic disorder characterized by a severe microcephaly with abnormal gyral pattern, severe growth retardation, bone abnormalities and a reduced life span for the most severe cases. It is caused by mutations in RNU4ATAC whose transcript, the small nuclear RNA U4atac, is a core component of the minor spliceosome involved in the excision of minor introns spread over ∼750 genes.Here, we report a patient presenting with TALS features but no mutation in RNU4ATAC ; instead, she carries the RTTN c.2953A>G variant at the homozygous state. This variant, already reported in patients with syndromic microcephaly, encodes the missense p.Arg985Gly amino acid change. It is also known to affect RTTN pre-mRNA splicing, with the expression of two forms lacking either exon 23 (in-frame) or exons 22-23 (out-of-frame). By using the engineered RTTN depleted RPE1 cellular model, we analysed independently the impact of the missense and in-frame deletion of exon 23 RTTN isoforms on the localisation and function of the protein at the centrosome, and showed that the pathogenicity of the c.2953A>G variant is mostly due to the latter. In patient fibroblasts, we observed a reduction of the centriole length and an alteration of ciliary function, while the analysis of neuronal stem cells (NSC) derived from CRISPR/Cas9-edited induced pluripotent stem cells revealed major cell cycle and mitotic abnormalities, leading to aneuploidy, cell cycle arrest and increased cell death. Finally, by generating cortical organoids, we discovered a new function of RTTN in the self-organisation of NSC into neural rosettes. We observed a delayed apico-basal polarization of NSC, accompanied with decreased cell division and increased apoptosis. Altogether, these defects lead to a marked decrease of rosette number and size in RTTN -mutated organoids, thus impeding their overall growth.To conclude, our study gives new insights on microcephaly-related pathophysiological mechanisms underlying the only recurrent RTTN mutation, that could also open a path to better understand those involved in RNU4ATAC -associated Taybi-Linder syndrome.### Competing Interest StatementThe authors have declared no competing interest.### Funding StatementThis work was supported by CNRS, Inserm and Universite Lyon 1 through recurrent funding; the Agence Nationale de la Recherche (no. ANR-18CE12-0007; no. ANR-22CE12-0007); the Fondation Jerome Lejeune and the Fondation pour la recherche sur le Cerveau "Espoir en tete" (confocal microscope). J.G. was supported by the Ministere de l'Enseignement Superieur et de la Recherche and by the Fondation pour la Recherche Medicale. T-Y C. was supported by a postdoctoral fellowship from Academia Sinica, Taiwan and T.K.T by the National Science and Technology Council (NSTC 112-2326-B001-010) and Academia Sinica (AS-IA-109-L04), Taiwan. E.B. was supported by an EMBO long-term fellowship (ALTF-284-2019), and V.H. by the Swiss National Foundation (SNSF) 310030_205087. S.T. was supported by Agence Nationale de la Recherche (no. ANR-17-CE16-0003-01).### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:French national ethical committee Comite de Protection des Personnes (number 2021-A01551-40) gave ethical approval for this work.I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesAll data produced in the present study are available upon reasonable request to the authors

Minimizing interfacial charged traps in perovskite films is crucial for reducing the non-radiative recombination and improving device performance. In this study, succinic acid (SA) derivatives varying active sites and spatial configurations are designed to modulate defects and crystallization in perovskite film. The SA derivative with two symmetric Br atoms, dibromosuccinic acid (DBSA), exhibits the optimal spatial arrangement for defect passivation. Experimental and theoretical results indicate that the carboxyl group and atomic Br in DBSA synergistically interact with the under-coordinated Pb2+ . Moreover, the strong electronegativity of Br efficiently stabilizes the formamidinium cation via electrostatic interaction. Consequently, film quality is significantly improved and non-radiative recombination is markedly depressed, resulting in a photoluminesence lifetime of exceeding 4 µs of and a carrier diffusion length of 3 µm. An exceptional efficiency of 25.41% (certified at 25.00%) along with a high fill factor of 84.39% and excellent long-term operational stability have been achieved finally.

Desirable crystal growth and defect modulation of Br-free RbCsFAMA perovskite films have been achieved by introducing an aromatic zwitterion, giving the record efficiencies of 25.01% and 23.40% for devices with areas of 0.09 cm2 and 1 cm2.

Regulating the charge extraction ability of electron transport materials and constructing a chemically linked interface are imperative to enhance the power conversion efficiencies (PCEs) and improve the device stability of perovskite solar cells (PSCs). Herein, a heterocyclic amino acid molecule of 3-amino-4-pyrazolecarboxylic acid (APA) is incorporated into the SnO2/perovskite interface to improve the device performance via a multifunctional interfacial bridge. The carboxylic group and pyrazole N in APA significantly improve the optoelectronic properties of SnO2, such as carrier mobility, conductivity, energy levels and trap-state. Meanwhile, the pre-buried APA effectively passivates the buried perovskite interface, enhances the crystallinity of perovsite film and boosts the carrier extraction efficiency through chemically linking SnO2 and perovskite. As a result, the champion device delivers an impressive PCE of 24.71 % along with a fill factor of 83.56 %, which is one of the highest efficiencies for RbCsFAMA quadruple cation PSCs. Moreover, over 83 % and 80 % of their initial efficiencies are retained after 2400 h of storage and 500 h of continuous maximum output power point tracking under 1 sun illumination (white light LED array) for the unencapsulated devices, respectively. This work offers a facile approach to construct a robust interfacial bridge for efficient and stable PSCs.

The carrier extraction and transportation capability of electron-selective layers and light-absorbers are very important for achieving highly efficient perovskite solar cells (PSCs). Herein, a holistic approach to boost the carrier transportation in a SnO2/perovskite stack is presented. First, the optoelectronic properties of SnO2, such as carrier mobility, conductivity, energy levels and trap states, are effectively regulated via a Nb5+ and Ta5+ co-doping strategy (denoted as NT:SnO2). Meanwhile, the upgraded SnO2 modulates the subsequent crystallization of perovskites, resulting in enhanced crystallinity. Second, a multifunctional molecule of 4,4 '-dithiodibutyric acid is selected to further passivate the charged-traps in perovskites, leading to significantly decreased non-radiative recombination and an increased carrier lifetime of over 3 mu s. Finally, the champion device consisted of NT:SnO2 and the optimized perovskite film delivered an impressive PCE of 25.30% along with a high fill factor of 84.51%, which is among the highest efficiencies for RbCsFAMA-based PSCs to date. The target device without encapsulation also shows excellent long-term operational stability, over 90% of its initial efficiency is retained after 1200 h of continuous maximum output power point tracking under 1 sun illumination. This study will pave a new avenue for managing the carrier behavior in a SnO2/perovskite stack and realizing highly efficient and stable PSCs. Metal ion co-doping and additive-mediation strategies were used to boost the carrier extraction and transportation in a SnO2/perovskite stack, resulting in 25.30% efficiency for perovskite solar cells along with outstanding device stability.

Melatonin is a functionally conserved broad-spectrum physiological regulator found in most biological organisms in nature. Enrichment of tomato fruit with melatonin not only enhances its agronomic traits but also provides extra health benefits. In this study, we elucidate the full melatonin biosynthesis pathway in tomato fruit by identifying biosynthesis-related genes that encode caffeic acid O-methyltransferase 2 (SlCOMT2) and N-acetyl-5-hydroxytryptamine-methyltransferases 5/7 (SlASMT5/7). We further reveal that red light supplementation significantly enhances the melatonin content in tomato fruit. This induction relies on the "serotonin-N-acetylserotonin-melatonin" biosynthesis route via the SlphyB2-SlPIF4-SlCOMT2 module. Based on the regulatory mechanism, we design a gene-editing strategy to target the binding motif of SlPIF4 in the promoter of SlCOMT2, which significantly enhances the production of melatonin in tomato fruit. Our study provides a good example of how the understanding of plant metabolic pathways responding to environmental factors can guide the engineering of health-promoting foods.

Both improving crystallization and passivating the defects of a perovskite film have been realized by introducing 2-amidinopyrimidine hydrochloride, which resulted in an efficiency of 25.17% along with long-term operational stability.

Herein, the aspects of ion migration in polycrystalline CH3NH3PbBr3 thin film and their phenomenal influences on the output performance of perovskite light-emitting diodes (PeLEDs) are reported. The physical insight of bias-induced migration of mobile ions in the perovskite active layer effectuating the observed non-linearity in the increased magnitude of electroluminescence (EL) and luminous efficiency (LE) as a function of current density for PeLEDs is directly evidenced using the capacitance spectroscopy. Adding the zwitterion molecule, Choline chloride (Ch.Cl), in CH3NH3PbBr3 precursor solution for preparing polycrystalline perovskite film effectively passivates the charged defects, either positively or negatively, in organic-inorganic halide perovskite and most importantly interferes the migration of ions crossing the grains in PeLEDs as verified by the higher calculated magnitude of the activation energy for the migration of mobile ions. As a result, the Ch.Cl-additive devices exhibit the rather stable EL and LE magnitude under the electric bias. EL magnitude increases linearly as a function of current density, revealing the epitome of output characteristics for decent light-emitting diodes. To suppress the influence of the migrating ions on operating PeLEDs is a key issue before it is stepped further to advance the efficiencies and the operational stabilities of perovskite devices.