Pacer Is a Mediator of mTORC1 and GSK3-TIP60 Signaling in Regulation of Autophagosome Maturation and Lipid Metabolism.

mTORC1 and GSK3 play critical roles in early stages of (macro)autophagy, but how they regulate late steps of autophagy remains poorly understood. Here we show that mTORC1 and GSK3-TIP60 signaling converge to modulate autophagosome maturation through Pacer, an autophagy regulator that was identified in our recent study. Hepatocyte-specific Pacer knockout in mice results in impaired autophagy flux, glycogen and lipid accumulation, and liver fibrosis. Under nutrient-rich conditions, mTORC1 phosphorylates Pacer at serine157 to disrupt the association of Pacer with Stx17 and the HOPS complex and thus abolishes Pacer-mediated autophagosome maturation. Importantly, dephosphorylation of Pacer under nutrient-deprived conditions promotes TIP60-mediated Pacer acetylation, which facilitates HOPS complex recruitment and is required for autophagosome maturation and lipid droplet clearance. This work not only identifies Pacer as a regulator in hepatic autophagy and liver homeostasis in vivo but also reveals a signal integration mechanism involved in late stages of autophagy and lipid metabolism.

A machine learning-based framework for mapping hydrogen at the atomic scale.

Hydrogen, the lightest and most abundant element in the universe, plays essential roles in a variety of clean energy technologies and industrial processes. For over a century, it has been known that hydrogen can significantly degrade the mechanical properties of materials, leading to issues like hydrogen embrittlement. A major challenge that has significantly limited scientific advances in this field is that light atoms like hydrogen are difficult to image, even with state-of-the-art microscopic techniques. To address this challenge, here, we introduce Atom-H, a versatile and generalizable machine learning-based framework for imaging hydrogen atoms at the atomic scale. Using a high-resolution electron microscope image as input, Atom-H accurately captures the distribution of hydrogen atoms and local stresses at lattice defects, including dislocations, grain boundaries, cracks, and phase boundaries. This provides atomic-scale insights into hydrogen-governed mechanical behaviors in metallic materials, including pure metals like Ni, Fe, Ti and alloys like FeCr. The proposed framework has an immediate impact on current research into hydrogen embrittlement and is expected to have far-reaching implications for mapping "invisible" atoms in other scientific disciplines.

Grain boundary plasticity initiated by excess volume.

Grain boundaries (GBs) serve not only as strong barriers to dislocation motion, but also as important carriers to accommodate plastic deformation in crystalline solids. During deformation, the inherent excess volume associated with loose atomic packing in GBs brings about a microscopic degree of freedom that can initiate GB plasticity, which is beyond the classic geometric description of GBs. However, identification of this atomistic process has long remained elusive due to its transient nature. Here, we use Au polycrystals to unveil a general and inherent route to initiating GB plasticity via a transient topological transition process triggered by the excess volume. This route underscores the general impact of a microscopic degree of freedom which is governed by a stress-triaxiality-based criterion. Our findings provide a missing perspective for developing a more comprehensive understanding of the role of GBs in plastic deformation.

Single-cell transcriptome and metagenome profiling reveals the genetic basis of rumen functions and convergent developmental patterns in ruminants.

The rumen undergoes developmental changes during maturation. To characterize this understudied dynamic process, we profiled single-cell transcriptomes of about 308,000 cells from the rumen tissues of sheep and goats at 17 time points. We built comprehensive transcriptome and metagenome atlases from early embryonic to rumination stages, and recapitulated histomorphometric and transcriptional features of the rumen, revealing key transitional signatures associated with the development of ruminal cells, microbiota, and core transcriptional regulatory networks. In addition, we identified and validated potential cross-talk between host cells and microbiomes and revealed their roles in modulating the spatiotemporal expression of key genes in ruminal cells. Cross-species analyses revealed convergent developmental patterns of cellular heterogeneity, gene expression, and cell-cell and microbiome-cell interactions. Finally, we uncovered how the interactions can act upon the symbiotic rumen system to modify the processes of fermentation, fiber digestion, and immune defense. These results significantly enhance understanding of the genetic basis of the unique roles of rumen.

ER membrane complex (EMC): Structure, functions, and roles in diseases.

The endoplasmic reticulum (ER) is the largest membrane system in eukaryotic cells and is the primary site for the biosynthesis of lipids and carbohydrates, as well as for the folding, assembly, modification, and transport of secreted and integrated membrane proteins. The ER membrane complex (EMC) on the ER membrane is an ER multiprotein complex that affects the quality control of membrane proteins, which is abundant and widely preserved. Its disruption has been found to affect a wide range of processes, including protein and lipid synthesis, organelle communication, endoplasmic reticulum stress, and viral maturation, and may lead to neurodevelopmental disorders and cancer. Therefore, EMC has attracted the attention of many scholars and become a hot field. In this paper, we summarized the main contributions of the research of EMC in the past nearly 15 years, and reviewed the structure and function of EMC as well as its related diseases. We hope this review will promote further progress of research on EMC.

Tankyrases inhibit innate antiviral response by PARylating VISA/MAVS and priming it for RNF146-mediated ubiquitination and degradation.

During viral infection, sensing of viral RNA by retinoic acid-inducible gene-I-like receptors (RLRs) initiates an antiviral innate immune response, which is mediated by the mitochondrial adaptor protein VISA (virus-induced signal adaptor; also known as mitochondrial antiviral signaling protein [MAVS]). VISA is regulated by various posttranslational modifications (PTMs), such as polyubiquitination, phosphorylation, O-linked ß-d-N-acetylglucosaminylation (O-GlcNAcylation), and monomethylation. However, whether other forms of PTMs regulate VISA-mediated innate immune signaling remains elusive. Here, we report that Poly(ADP-ribosyl)ation (PARylation) is a PTM of VISA, which attenuates innate immune response to RNA viruses. Using a biochemical purification approach, we identified tankyrase 1 (TNKS1) as a VISA-associated protein. Viral infection led to the induction of TNKS1 and its homolog TNKS2, which translocated from cytosol to mitochondria and interacted with VISA. TNKS1 and TNKS2 catalyze the PARylation of VISA at Glu137 residue, thereby priming it for K48-linked polyubiquitination by the E3 ligase Ring figure protein 146 (RNF146) and subsequent degradation. Consistently, TNKS1, TNKS2, or RNF146 deficiency increased the RNA virus-triggered induction of downstream effector genes and impaired the replication of the virus. Moreover, TNKS1- or TNKS2-deficient mice produced higher levels of type I interferons (IFNs) and proinflammatory cytokines after virus infection and markedly reduced virus loads in the brains and lungs. Together, our findings uncover an essential role of PARylation of VISA in virus-triggered innate immune signaling, which represents a mechanism to avoid excessive harmful immune response.

Controllable Pseudoelasticity in Metallic Nanocrystals by Grain Boundary Engineering.

Materials with pseudoelasticity can recover from large strains exceeding their elastic limits during unloading, making them promising damage-tolerant building blocks for advanced nanodevices. Nevertheless, a practical approach to realize controllable pseudoelastic behavior at nanoscale remains challenging. Here, we proposed a grain boundary (GB) engineering approach to endow metallic nanocrystals with a controllable pseudoelasticity. Both in situ nanomechanical testing and atomistic simulations demonstrate that such controllable pseudoelasticity is governed by the extension and contraction of an inherent stacking fault array at the GB. By precisely tuning GB misorientation and inclination, our simulation results reveal that metallic nanocrystals can exhibit tailored pseudoelastic performance across a broad spectrum of GBs in different face-centered cubic metals. These findings enrich our understanding of the intrinsic pseudoelasticity of GBs and provide a GB engineering approach toward metallic materials with reversible deformability.

Dynamic cerebellar and sensorimotor network compensation in tremor-dominated Parkinson's disease.

AIM: Parkinson's disease (PD) tremor is associated with dysfunction in the basal ganglia (BG), cerebellum (CB), and sensorimotor networks (SMN). We investigated tremor-related static functional network connectivity (SFNC) and dynamic functional network connectivity (DFNC) in PD patients. METHODS: We analyzed the resting-state functional MRI data of 21 tremor-dominant Parkinson's disease (TDPD) patients and 29 healthy controls. We compared DFNC and SFNC between the three networks and assessed their associations with tremor severity. RESULTS: TDPD patients exhibited increased SFNC between the SMN and BG networks. In addition, they spent more mean dwell time (MDT) in state 2, characterized by sparse connections, and less MDT in state 4, indicating stronger connections. Furthermore, enhanced DFNC between the CB and SMN was observed in state 2. Notably, the MDT of state 2 was positively associated with tremor scores. CONCLUSION: The enhanced dynamic connectivity between the CB and SMN in TDPD patients suggests a potential compensatory mechanism. However, the tendency to remain in a state of sparse connectivity may contribute to the severity of tremor symptoms.

FAM134B oligomerization drives endoplasmic reticulum membrane scission for ER-phagy.

Degradation of endoplasmic reticulum (ER) by selective autophagy (ER-phagy) is crucial for ER homeostasis. However, it remains unclear how ER scission is regulated for subsequent autophagosomal sequestration and lysosomal degradation. Here, we show that oligomerization of ER-phagy receptor FAM134B (also referred to as reticulophagy regulator 1 or RETREG1) through its reticulon-homology domain is required for membrane fragmentation in vitro and ER-phagy in vivo. Under ER-stress conditions, activated CAMK2B phosphorylates the reticulon-homology domain of FAM134B, which enhances FAM134B oligomerization and activity in membrane fragmentation to accommodate high demand for ER-phagy. Unexpectedly, FAM134B G216R, a variant derived from a type II hereditary sensory and autonomic neuropathy (HSAN) patient, exhibits gain-of-function defects, such as hyperactive self-association and membrane scission, which results in excessive ER-phagy and sensory neuron death. Therefore, this study reveals a mechanism of ER membrane fragmentation in ER-phagy, along with a signaling pathway in regulating ER turnover, and suggests a potential implication of excessive selective autophagy in human diseases.

Interbrain substrates of role switching during mother-child interaction.

Mother-child interaction is highly dynamic and reciprocal. Switching roles in these back-and-forth interactions serves as a crucial feature of reciprocal behaviors while the underlying neural entrainment is still not well-studied. Here, we designed a role-controlled cooperative task with dual EEG recording to explore how differently two brains interact when mothers and children hold different roles. When children were actors and mothers were observers, mother-child interbrain synchrony emerged primarily within the theta oscillations and the frontal lobe, which highly correlated with children's attachment to their mothers (self-reported by mothers). When their roles were reversed, this synchrony was shifted to the alpha oscillations and the central area and associated with mothers' perception of their relationship with their children. The results suggested an observer-actor neural alignment within the actor's oscillations, which was related to the actor-toward-observer emotional bonding. Our findings contribute to the understanding of how interbrain synchrony is established and dynamically changed during mother-child reciprocal interaction.

Fluorescent Dye-Based Chiral Crystalline Organic Salt Networks for Circularly Polarized Luminescence.

A facile and general strategy is developed herein for the construction of circularly polarized luminescence (CPL) materials with simultaneously high fluorescence quantum efficiency (Φ) and large luminescence dissymmetry factor (glum). The self-assembly of fluorescent dye, disodium 4,4'-bis(2-sulfonatostyryl)biphenyl (CBS), with chiral diamines such as (R,R)/(S,S)-1,2-diaminocyclohexane (R/S-DACH) and R/S-1,2-diaminopropane (R/S-DAP), produces four chiral crystalline organic salt networks (COSNs). These as-synthesized organic salts emit strong blue-color CPL upon excitation, with both high Φ and glum values of up to 79% and 0.022. The well-defined molecular structures and arrangements of CBS are directly observed through single crystal X-ray analysis, offering crucial information regarding the origins of high-efficiency CPL performance. The chirality of amine is effectively transferred to CBS and further amplified to the supramolecular structure by multiple hydrogen bonding and π-π stacking interactions, giving rise to the large glum factors; meanwhile, the fixation and the ordered arrangement of CBS by these multiple interactions empower efficient suppression of molecular motions, facilitating strong fluorescence. This work can inspire the assembly of CPL organic materials with high Φ and glum via charge-assisted hydrogen bonds between fluorescent dyes and chiral inducers. It also offers important insight into the structural origins of supramolecular chirality and CPL performance.

Breaking Through the Trade-Off Between Wide Band Gap and Large SHG Coefficient in Mercury-Based Chalcogenides for IR Nonlinear Optical Application.

It is substantially challenging for non-centrosymmetric (NCS) Hg-based chalcogenides for infrared nonlinear optical (IR-NLO) applications to realize wide band gap (Eg > 3.0 eV) and sufficient phase-matching (PM) second-harmonic-generation intensity (deff > 1.0 × benchmark AgGaS2 ) simultaneously due to the inherent incompatibility. To address this issue, this work presents a diagonal synergetic substitution strategy for creating two new NCS quaternary Hg-based chalcogenides, AEHgGeS4 (AE = Sr and Ba), based on the centrosymmetric (CS) AEIn2 S4 . The derived AEHgGeS4 displays excellent NLO properties such as a wide Eg (≈3.04-3.07 eV), large PM deff (≈2.2-3.0 × AgGaS2 ), ultra-high laser-induced damage threshold (≈14.8-15 × AgGaS2 ), and suitable Δn (≈0.19-0.24@2050 nm), making them highly promising candidates for IR-NLO applications. Importantly, such excellent second-order NLO properties are primarily attributed to the synergistic combination of tetrahedral [HgS4 ] and [GeS4 ] functional primitives, as supported by detailed theoretical calculations. This study reports the first two NCS Hg-based materials with well-balanced comprehensive properties (i.e., Eg > 3.0 eV and deff > 1.0 × benchmark AgGaS2 ) and puts forward a new design avenue for the construction of more efficient IR-NLO candidates.

Ubiquitin-specific protease 14 targets PFKL-mediated glycolysis to promote the proliferation and migration of oral squamous cell carcinoma.

Aberrant upregulation of the ubiquitin-specific protease 14 (USP14) has been found in some malignant tumors, including oral squamous cell carcinoma (OSCC). In this study, we further demonstrated that aberrantly overexpressed USP14 was also closely related to adverse clinicopathological features and poor prognosis in patients with OSCC, so we hypothesized that USP14 might act as a tumor-promoting factor during the progression of OSCC. Notably, we originally proved that USP14 is a deubiquitinating enzyme for phosphofructokinase-1 liver type (PFKL), a key rate-limiting enzyme involved in the glycolytic pathway. USP14 interacts with PFKL and enhances its stability through deubiquitination in OSCC cells, which in turn enhances PFKL-mediated glycolytic metabolism and ultimately promote cellular proliferation, migration, and tumorigenesis. In this work, we have also demonstrated for the first time that USP14 is a critical regulator of glycolysis in OSCC and verified a novel mechanism whereby it is involved in tumor metastasis and growth. Collectively, our findings provide novel insights into the tumor-promoting role of USP14 and establish mechanistic foundations for USP14-targeting therapies.

Single-cell RNA sequencing reveals the effects of high-fat diet on oocyte and early embryo development in female mice.

BACKGROUND: Obesity is a global health issue with detrimental effects on various human organs, including the reproductive system. Observational human data and several lines of animal experimental data suggest that maternal obesity impairs ovarian function and early embryo development, but the precise pathogenesis remains unclear. METHODS: We established a high-fat diet (HFD)-induced obese female mouse model to assess systemic metabolism, ovarian morphology, and oocyte function in mice. For the first time, this study employed single-cell RNA sequencing to explore the altered transcriptomic landscape of preimplantation embryos at different stages in HFD-induced obese mice. Differential gene expression analysis, enrichment analysis and protein-protein interactions network analysis were performed. RESULTS: HFD-induced obese female mice exhibited impaired glucolipid metabolism and insulin resistance. The ovaries of HFD mice had a reduced total follicle number, an increased proportion of atretic follicles, and irregular granulosa cell arrangement. Furthermore, the maturation rate of embryonic development by in vitro fertilization of oocytes was significantly decreased in HFD mice. Additionally, the transcriptional landscapes of preimplantation embryos at different stages in mice induced by different diets were significantly distinguished. The maternal-to-zygotic transition was also affected by the failure to remove maternal RNAs and to turn off zygotic genome expression. CONCLUSIONS: HFD-induced obesity impaired ovarian morphology and oocyte function in female mice and further led to alterations in the transcriptional landscape of preimplantation embryos at different stages of HFD mice.

New evidence: Metformin unsuitable as routine adjuvant for breast cancer: a drug-target mendelian randomization analysis.

PURPOSE: The potential efficacy of metformin in breast cancer (BC) has been hotly discussed but never conclusive. This genetics-based study aimed to evaluate the relationships between metformin targets and BC risk. METHODS: Metformin targets from DrugBank and genome-wide association study (GWAS) data from IEU OpenGWAS and FinnGen were used to investigate the breast cancer (BC)-metformin causal link with various Mendelian Randomization (MR) methods (e.g., inverse-variance-weighting). The genetic association between type 2 diabetes (T2D) and the drug target of metformin was also analyzed as a positive control. Sensitivity and pleiotropic tests ensured reliability. RESULTS: The primary targets of metformin are PRKAB1, ETFDH and GPD1L. We found a causal association between PRKAB1 and T2D (odds ratio [OR] 0.959, P = 0.002), but no causal relationship was observed between metformin targets and overall BC risk (PRKAB1: OR 0.990, P = 0.530; ETFDH: OR 0.986, P = 0.592; GPD1L: OR 1.002, P = 0.806). A noteworthy causal relationship was observed between ETFDH and estrogen receptor (ER)-positive BC (OR 0.867, P = 0.018), and between GPD1L and human epidermal growth factor receptor 2 (HER2)-negative BC (OR 0.966, P = 0.040). Other group analyses did not yield positive results. CONCLUSION: The star target of metformin, PRKAB1, does not exhibit a substantial causal association with the risk of BC. Conversely, metformin, acting as an inhibitor of ETFDH and GPD1L, may potentially elevate the likelihood of developing ER-positive BC and HER2-negative BC. Consequently, it is not advisable to employ metformin as a standard supplementary therapy for BC patients without T2D.

Endoplasmic reticulum stress-mediated ferroptosis in granulosa cells contributes to follicular dysfunction of polycystic ovary syndrome driven by hyperandrogenism.

RESEARCH QUESTION: Does hyperandrogenaemia affect the function of ovarian granulosa cells by activating ferroptosis, and could this process be regulated by endoplasmic reticulum stress? DESIGN: Levels of ferroptosis and endoplasmic reticulum stress in granulosa cells were detected in women with and without polycystic ovary syndrome (PCOS) undergoing IVF. Ferroptosis and endoplasmic reticulum stress levels of ovarian tissue and follicle development were detected in control mice and PCOS-like mice models, induced by dehydroepiandrosterone. An in-vitro PCOS model of KGN cells was constructed with testosterone and ferroptosis inhibitor Fer-1. Endoplasmic reticulum stress inhibitor, tauroursodeoxycholate (TUDCA), determined the potential mechanism associated with excessive induction of ferroptosis in granulosa cells related to PCOS, and levels of ferroptosis and endoplasmic reticulum stress were detected. RESULTS: Activation of ferroptosis and endoplasmic reticulum stress occurred in granulosa cells of women with PCOS and the varies of PCOS-like mice. The findings in KGN cells demonstrated that testosterone treatment results in elevation of oxidative stress levels, particularly lipid peroxidation, and intracellular iron accumulation in granulosa cells. The expression of genes and proteins associated with factors related to ferroptosis, mitochondrial membrane potential and ultrastructure showed that testosterone activated ferroptosis, whereas Fer-1 reversed these alterations. During in-vitro experiments, activation of endoplasmic reticulum stress induced by testosterone treatment was detected in granulosa cells. In granulosa cells, TUDCA, an inhibitor of endoplasmic reticulum stress, significantly mitigated testosterone-induced ferroptosis. CONCLUSIONS: Ferroptosis plays a part in reproductive injury mediated by hyperandrogens associated with PCOS, and may be regulated by endoplasmic reticulum stress.

Utidelone plus pembrolizumab as the fourth-line combination treatment in non-small cell lung cancer with EGFR mutation: a case report.

Utidelone is an ebomycin derivative chemotherapeutic drug, which can promote tubulin polymerization and stabilize microtubule structure, so as to induce apoptosis. The drug is an innovative drug independently developed by China with independent intellectual property rights. Phase II clinical trials for advanced breast cancer are being approved by National Medical Products Administration for the treatment of advanced breast cancer. However, there is no report on the application in non-small cell lung cancer (NSCLC) patients with the epidermal growth factor receptor (EGFR) mutation. This case is a patient with EGFR mutant stage IV NSCLC who has progressed after third-line targeted therapy. The fourth line was treated with utidelone combined with pabolizumab. The patient had progressed after targeted therapy with oxitinib, ametinib, and vometinib. Due to the patient's physical reasons, the traditional platinum drugs were not suitable, so the patient was treated with utidelone combined with pabolizumab. The curative effect was evaluated as SD after two cycles and progesterone receptor after four cycles. At present, it is still in the maintenance of reduction of utidelone combined with pabolizumab, and the tumor continues to shrink. Although peripheral neurotoxicity occurred during treatment, it improved after symptomatic treatment. The treatment of EGFR mutant stage IV NSCLC with utidelone combined with pabolizumab has good effect and mild adverse reactions.

Evaluation of an oral small-molecule glucagon-like peptide-1 receptor agonist, lotiglipron, for type 2 diabetes and obesity: A dose-ranging, phase 2, randomized, placebo-controlled study.

AIM: The aim was to investigate the effects of lotiglipron, a once-daily, oral small-molecule glucagon-like peptide-1 (GLP-1) receptor agonist, in participants with type 2 diabetes (T2D) or obesity. MATERIALS AND METHODS: A phase 2, randomized, double-blind, placebo-controlled, dose-ranging study investigated the efficacy and safety of lotiglipron. The study was terminated early for safety reasons after routine data and monitoring review. The planned analyses for the end points were modified prior to unblinding the study. RESULTS: In total, 901 participants were treated with at least one dose of the study drug (T2D cohort: n = 512, obesity cohort: n = 389). Although the majority of participants who were randomly assigned to higher doses did not reach their target maintenance dose, statistically significant changes in HbA1c and body weight were observed. In the T2D cohort, reductions in HbA1c were observed across all lotiglipron doses at week 16 (p < 0.0001), with least squares mean decreases up to -1.44% (90% confidence interval [CI]: -1.63, -1.26) (lotiglipron 80 mg), versus placebo, -0.07% (90% CI: -0.25, 0.11). In the obesity cohort, decreases in body weight were observed across all lotiglipron doses at week 20 (p < 0.01), up to -7.47% (90% CI: -8.50, -6.43) (lotiglipron 200 mg, five-step titration), versus placebo, -1.84% (90% CI: -2.85, -0.83). Across cohorts, the most frequently reported treatment-emergent adverse events were gastrointestinal related (most mild to moderate severity), with nausea being the most common (ranging from 4% [placebo] to 28.8% [80 mg] in the T2D cohort and 12.5% [placebo] to 60.6% [200 mg, four-step titration] in the obesity cohort). Transaminase elevations were observed in a subset of participants (6.6% and 6.0% of participants on lotiglipron in the T2D and obesity cohorts, respectively, compared with 1.6% on placebo in the obesity cohort). CONCLUSIONS: The efficacy (HbA1c and/or body weight) of a range of lotiglipron doses was demonstrated in T2D and obesity cohorts. The safety profile was largely consistent with what has been previously known about the mechanism of action. Our results are unique in reporting elevations in liver transaminases in a subset of participants treated with lotiglipron, with attempts to identify the at-risk population unsuccessful and therefore clinical development of lotiglipron terminated. CLINICALTRIALS: GOV: NCT05579977.

Transition-Metal-Free Late-Stage Decarboxylative gem-Difluoroallylation of Primary Alkyl Acids.

A transition-metal-free late-stage decarboxylative gem-difluoroallylation of carboxylic acids with α-trifluoromethyl alkenes has been described by the use of organo-photoredox catalysis. Both primary alkyl and heteroaryl acids were readily incorporated. This approach merits feedstock materials, mild reaction conditions, and wide functionality tolerance. The synthetic utility of this approach has been highlighted by the late-stage functionalization of a variety of acid-containing natural products and drug molecules.

Ba10In2Mn11Si3O12S18: First Hexanary Oxychalcogenide Containing an Infrequent Three-Dimensional Noncentrosysmmetric Framework.

Noncentrosymmetric (NCS) oxychalcogenides have attracted great attention in recent years due to their immense potential as candidates for IR nonlinear-optical (NLO) applications. Despite notable advancements in this field, the discovery of oxychalcogenides with three-dimensional (3D) framework structures remains a formidable challenge. In this study, we report the discovery of the first hexanary oxychalcogenide, Ba10In2Mn11Si3O12S18, exhibiting second-order NLO activity, using a high-temperature solid-phase method. This compound showcases a novel structure type, featuring an uncommon NCS 3D [In2Mn11Si3O12S18]20- framework formed by vertex-sharing [(Mn/In)S6] octahedra, [(Mn/In)OS3] tetrahedra, and [SiO4] tetrahedra, with charge-balanced Ba2+ cations occupying the channels. Our study serves as a source of inspiration for researchers to further investigate the synthesis of novel NLO-active oxychalcogenides with 3D frameworks.