Impact factors and obstetric outcomes of preeclampsia in twin pregnancies by prepregnancy body mass index: a six-year retrospective cohort study.

OBJECTIVES: Among many risk factors for preeclampsia (PE), prepregnancy body mass index (BMI) is one of few controllable factors. However, there is a lack of stratified analysis based on the prepregnancy BMI. This study aimed to determine the influencing factors for PE and assess the impact of PE on obstetric outcomes in twin pregnancies by prepregnancy BMI. METHODS: This was a retrospective cohort study between January 1, 2017, and December 31, 2022, in Southwest China. Impact factors and associations between PE and obstetric outcomes were analyzed separately for twin pregnancies with prepregnancy BMI < 24kg/m2 (non-overweight group) and BMI ≥ 24kg/m2 (overweight group). RESULTS: In total, 3602 twin pregnancies were included, of which, 672 women were allocated into the overweight group and 11.8% of them reported with PE; 2930 women were allocated into the non-overweight group, with a PE incidence of 5.6%. PE had a negative effect on birthweight and increased the incidence of neonatal intensive care unit admission in both the overweight and non-overweight groups (43.0% vs. 28.0%, p = .008; 45.7% vs. 29.1%, p < .001). Among overweight women, PE increased the proportion of postpartum hemorrhage (15.2% vs. 4.4%, p < .001). After adjustments, multivariate regression analysis showed that excessive gestational weight gain (aOR = 1.103, 95% CI: 1.056-1.152; aOR = 1.094, 95% CI: 1.064-1.126) and hypoproteinemia (aOR = 2.828, 95% CI: 1.501-5.330; aOR = 6.932, 95% CI: 4.819-9.971) were the shared risk factors for PE in both overweight and non-overweight groups. In overweight group, in vitro fertilization was the other risk factor (aOR = 2.713, 95% CI: 1.183-6.878), whereas dichorionic fertilization (aOR = 0.435, 95% CI: 0.193-0.976) and aspirin use during pregnancy (aOR = 0.456, 95% CI: 0.246-0.844) were protective factors. Additionally, anemia during pregnancy (aOR = 1.542, 95% CI: 1.090-2.180) and growth discordance in twins (aOR = 2.451, 95% CI: 1.215-4.205) were connected with an increased risk of PE only in non-overweight twin pregnancies. CONCLUSIONS: Both discrepancy and similarity of impact factors on developing PE were found between overweight and non-overweight twin pregnancies in this study. However, the dosage and initiation time of aspirin, as well as twin chorionicity on the occurrence of PE in two subgroups, are still debated.

Dynamic Metabolons Using Stimuli-Responsive Protein Cages.

Naturally evolved metabolons have the ability to assemble and disassemble in response to environmental stimuli, allowing for the rapid reorganization of chemical reactions in living cells to meet changing cellular needs. However, replicating such capability in synthetic metabolons remains a challenge due to our limited understanding of the mechanisms by which the assembly and disassembly of such naturally occurring multienzyme complexes are controlled. Here, we report the synthesis of chemical- and light-responsive protein cages for assembling synthetic metabolons, enabling the dynamic regulation of enzymatic reactions in living cells. Particularly, a chemically responsive domain was fused to a self-assembled protein cage subunit, generating engineered protein cages capable of displaying proteins containing cognate interaction domains on their surfaces in response to small molecular cues. Chemical-induced colocalization of sequential enzymes on protein cages enhances the specificity of the branched deoxyviolacein biosynthetic reactions by 2.6-fold. Further, by replacing the chemical-inducible domain with a light-inducible dimerization domain, we created an optogenetic protein cage capable of reversibly recruiting and releasing targeted proteins onto and from the exterior of the protein cages in tens of seconds by on-off of blue light. Tethering the optogenetic protein cages to membranes enables the formation of light-switchable, membrane-bound metabolons, which can repeatably recruit-release enzymes, leading to the manipulation of substrate utilization across membranes on demand. Our work demonstrates a powerful and versatile strategy for constructing dynamic metabolons in engineered living cells for efficient and controllable biocatalysis.

Molecular basis for curvature formation in SepF polymerization.

The self-assembly of proteins into curved structures plays an important role in many cellular processes. One good example of this phenomenon is observed in the septum-forming protein (SepF), which forms polymerized structures with uniform curvatures. SepF is essential for regulating the thickness of the septum during bacteria cell division. In Bacillus subtilis, SepF polymerization involves two distinct interfaces, the ß-ß and α-α interfaces, which define the assembly unit and contact interfaces, respectively. However, the mechanism of curvature formation in this step is not yet fully understood. In this study, we employed solid-state NMR (SSNMR) to compare the structures of cyclic wild-type SepF assemblies with linear assemblies resulting from a mutation of G137 on the ß-ß interface. Our results demonstrate that while the sequence differences arise from the internal assembly unit, the dramatic changes in the shape of the assemblies depend on the α-α interface between the units. We further provide atomic-level insights into how the angular variation of the α2 helix on the α-α interface affects the curvature of the assemblies, using a combination of SSNMR, cryo-electron microscopy, and simulation methods. Our findings shed light on the shape control of protein assemblies and emphasize the importance of interhelical contacts in retaining curvature.

Inhibitor screening for volume-sensitive LRRC8A chloride channel.

Leucine-rich repeat-containing protein 8 A (LRRC8A) protein is a critical member of volume-regulated anion channels. It plays a critical roles in the regulation of cellular volume and involves in the development of diseases like osteoarthritis. Screening of lead compounds to modulate its function may provide potential therapeutics of related diseases. Here, we employ virtual screening techniques and molecular dynamics (MD) simulation to screen potential inhibitors against LRRC8A. LRRC8A was regarded as the drug target to investigate potential compounds from the ZINC15 database via molecular docking. The final compound was selected among the top 10 Autodock Vina score (-8.8 Kcal/mol) with the ZINC ID ZINC000018195627 after druggability prediction. The docked complex from the virtual screening was subjected to MD simulation to analyze the stability of the LRRC8A protein-ligand complex, with parameters including root mean square deviation, root mean square fluctuation and radius of gyration. Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) method was further employed to predict the binding free energies from MD simulation trajectory. Our study provides insightful analysis for the potential compound to modulate LRRC8A and lay the foundation of therapeutics development against osteoarthritis.Communicated by Ramaswamy H. Sarma.

Analysis on the current situation of twin breastfeeding and its influencing factors.

Studies have found that exclusive breastfeeding can not only promote the growth and development of infants, but also increase the emotional communication between mothers and infants, and reduce the incidence of maternal breast diseases. To analysis the current situation and influencing factors of breastfeeding twins. A total of 420 twin mothers delivered in our hospital from January 2019 to December 2022 were selected to investigate the situation of breastfeeding within 6 months after delivery. An electronic questionnaire was conducted, and clinical information were collected. Univariate analysis and multivariate logistic regression analysis were applied to analyze the factors influencing exclusive breastfeeding. The rate of exclusive breastfeeding was 21.90%; in the exclusive breastfeeding group, the age <35 years old, bachelor degree or above, rural areas, no nipple depression or flat, no breast distension, no postpartum depression, adequate breast milk, participation in health education during pregnancy, husband support for breastfeeding, no infant feeding difficulties, infant diarrhea, lactose intolerance and return to milk were 96.74%, 53.26%, 65.22%, 80.43%, 76.09%, 80.43%, 73.91%, 63.04%, 69.57%, 71.74%, 65.22%, 70.65%, and 66.30%, respectively. It was significantly higher than that in the non-exclusive breastfeeding group (P < .05). The score of Edinburgh Postpartum Depression Scale (EPDS) was (8.08 ± 1.03) in the exclusive breastfeeding group, which was significantly lower than that in the non-exclusive breastfeeding group (P < .001), while the score of Perceived Social Support Scale (PSSS) was (67.32 ± 9.92), which was significantly higher than that in the non-exclusive breastfeeding one(P < .001). Logistic regression analysis showed that age, education level, nipple depression or flat, breast tenderness, postpartum depression, breast milk volume, health education training during pregnancy, husband support for breastfeeding, PSSS score, infant diarrhea, lactose intolerance, and delectation were the influencing factors of exclusive breastfeeding (P < .001). Our findings suggest that various factors were associated with a low rate of exclusive breastfeeding in twin births, such as age, educational level, and social support. Corresponding measures should be formulated for intervention to promote exclusive breastfeeding.

miR-182 promotes cervical cancer progression via activating the Wnt/ß-catenin axis.

Cervical cancer (CC) is among the leading causes of cancer-associated mortality in women worldwide; yet the molecular regulators involved in its progression are unclear. This study found that miR-182 was overexpressed in CC tissues when compared with adjacent normal tissues. Moreover, it found that miR-182 expression was significantly positively correlated with distant metastasis in patients with CC. Interestingly, in vitro experiments showed that overexpression and inhibition of miR-182 promoted and suppressed the growth of CC cells, respectively. The tumor-promoting effects of miR-182 on CC progression were achieved via the Wnt/ß-catenin axis and its downstream genes. Thus, this study revealed the potential of miR-182/ß-catenin as an effective new target for CC treatment.

[Retracted] MicroRNA­124 acts as a tumor­suppressive miRNA by inhibiting the expression of Snail2 in osteosarcoma.

[This retracts the article DOI: 10.3892/ol.2018.7994.].

One-step fabrication of cell sheet-laden hydrogel for accelerated wound healing.

Full-thickness skin wounds are have continued to be reconstructive challenges in dermal and skin appendage regeneration, and skin substitutes are promising tools for addressing these reconstructive procedures. Herein, the one-step fabrication of a cell sheet integrated with a biomimetic hydrogel as a tissue engineered skin for skin wound healing generated in one step is introduced. Briefly, cell sheets with rich extracellular matrix, high cell density, and good cell connections were integrated with biomimetic hydrogel to fabricate gel + human skin fibroblasts (HSFs) sheets and gel + human umbilical vein endothelial cells (HUVECs) sheets in one step for assembly as a cell sheet-laden hydrogel (CSH). The designed biomimetic hydrogel formed with UV crosslinking and ionic crosslinking exhibited unique properties due to the photo-generated aldehyde groups, which were suitable for integrating into the cell sheet, and ionic crosslinking reduced the adhesive force toward the substrate. These properties allowed the gel + cell sheet film to be easily released from the substrate. The cells in the harvested cell sheet maintained excellent viability, proliferation, and definite migration abilities inside the hydrogel. Moreover, the CSH was implanted into a full-thickness skin defects to construct a required dermal matrix and cell microenvironment. The wound closure rate reached 60.00 ± 6.26% on the 2nd day, accelerating mature granulation and dermis formation with skin appendages after 14 days. This project can provide distinct guidance and strategies for the complete repair and regeneration of full-thickness skin defects, and provides a material with great potential for tissue regeneration in clinical applications.

Cryo-EM structures of ClC-2 chloride channel reveal the blocking mechanism of its specific inhibitor AK-42.

ClC-2 transports chloride ions across plasma membranes and plays critical roles in cellular homeostasis. Its dysfunction is involved in diseases including leukodystrophy and primary aldosteronism. AK-42 was recently reported as a specific inhibitor of ClC-2. However, experimental structures are still missing to decipher its inhibition mechanism. Here, we present cryo-EM structures of apo ClC-2 and its complex with AK-42, both at 3.5 Å resolution. Residues S162, E205 and Y553 are involved in chloride binding and contribute to the ion selectivity. The side-chain of the gating glutamate E205 occupies the putative central chloride-binding site, indicating that our structure represents a closed state. Structural analysis, molecular dynamics and electrophysiological recordings identify key residues to interact with AK-42. Several AK-42 interacting residues are present in ClC-2 but not in other ClCs, providing a possible explanation for AK-42 specificity. Taken together, our results experimentally reveal the potential inhibition mechanism of ClC-2 inhibitor AK-42.

Gold Nanoparticles Reduce Food Sensation in Caenorhabditis elegans via the Voltage-Gated Channel EGL-19.

Introduction: The increasing use of gold nanoparticles (Au NPs) in the medical field has raised concerns about the potential adverse effect of Au NPs exposure. However, it is difficult to assess the health risks of Au NPs exposure at the individual organ level using current measurement techniques. Methods: The physical and chemical properties of Au NPs were characterized by transmission electron microscope (TEM), Fourier transform infrared (FTIR), and zeta sizer. The RNA-seq data of Au NPs-exposed worms were analyzed. The food intake was measured by liquid culture and Pharyngeal pumping rate. The function of the smell and taste neurons was evaluated by the chemotaxis and avoidance assay. The activation of ASE neurons was analyzed by calcium imaging. The gene expression of ins-22 and egl-19 was obtained from the C. elegans single cell RNA-seq databases. Results: Our data analysis indicated that 62.8% of the significantly altered genes were functional in the nervous system. Notably, developmental stage analysis demonstrated that exposure to Au NPs interfered with animal development by regulating foraging behavior. Also, our chemotaxis results showed that exposure to Au NPs reduced the sensation of C. elegans to NaCl, which was consistent with the decrease in calcium transit of ASEL. Further studies confirmed that the reduced calcium transit was dependent on voltage-gated calcium channel EGL-19. The neuropeptide INS-22 was partially involved in Au NPs-induced NaCl sensation defect. Therefore, we proposed that Au NPs reduced the calcium transit in the ASEL neuron through egl-19-dependent calcium channels. It was partially regulated by the DAF-16 targeting neuropeptide INS-22. Discussion: Our results demonstrate that Au NPs affect food sensation by reducing the calcium transit in ASEL neurons, which further leads to reduced pharynx pumping and feeding defects. The toxicology studies of Au NPs from worms have great potential to guide the usage of Au NPs in the medical field such as targeted drug delivery.

Applications and prospects of cryo-EM in drug discovery.

Drug discovery is a crucial part of human healthcare and has dramatically benefited human lifespan and life quality in recent centuries, however, it is usually time- and effort-consuming. Structural biology has been demonstrated as a powerful tool to accelerate drug development. Among different techniques, cryo-electron microscopy (cryo-EM) is emerging as the mainstream of structure determination of biomacromolecules in the past decade and has received increasing attention from the pharmaceutical industry. Although cryo-EM still has limitations in resolution, speed and throughput, a growing number of innovative drugs are being developed with the help of cryo-EM. Here, we aim to provide an overview of how cryo-EM techniques are applied to facilitate drug discovery. The development and typical workflow of cryo-EM technique will be briefly introduced, followed by its specific applications in structure-based drug design, fragment-based drug discovery, proteolysis targeting chimeras, antibody drug development and drug repurposing. Besides cryo-EM, drug discovery innovation usually involves other state-of-the-art techniques such as artificial intelligence (AI), which is increasingly active in diverse areas. The combination of cryo-EM and AI provides an opportunity to minimize limitations of cryo-EM such as automation, throughput and interpretation of medium-resolution maps, and tends to be the new direction of future development of cryo-EM. The rapid development of cryo-EM will make it as an indispensable part of modern drug discovery.

Cryo-EM structure of human heptameric pannexin 2 channel.

Pannexin 2 (Panx2) is a large-pore ATP-permeable channel with critical roles in various physiological processes, such as the inflammatory response, energy production and apoptosis. Its dysfunction is related to numerous pathological conditions including ischemic brain injury, glioma and glioblastoma multiforme. However, the working mechanism of Panx2 remains unclear. Here, we present the cryo-electron microscopy structure of human Panx2 at a resolution of 3.4 Å. Panx2 structure assembles as a heptamer, forming an exceptionally wide channel pore across the transmembrane and intracellular domains, which is compatible with ATP permeation. Comparing Panx2 with Panx1 structures in different states reveals that the Panx2 structure corresponds to an open channel state. A ring of seven arginine residues located at the extracellular entrance forms the narrowest site of the channel, which serves as the critical molecular filter controlling the permeation of substrate molecules. This is further verified by molecular dynamics simulations and ATP release assays. Our studies reveal the architecture of the Panx2 channel and provide insights into the molecular mechanism of its channel gating.

The Risk Factors for New-Onset Calf Muscle Venous Thrombosis after Hip Fracture Surgery.

BACKGROUND: Calf muscle venous thrombosis (CMVT) is among the most important medical complications after hip surgery. CMVT has been known for many years, but many opinions about the incidence and risk factors of CMVT are still controversial. The objective of this retrospective study was to investigate the incidence and associated risk factors of postoperative CMVT in patients with hip fractures. METHODS: Patients with hip fractures from January 2020 to April 2022 (n = 320) at Shenzhen Second People's Hospital were recruited in this study. The personal characteristics and clinical data of CMVT and no-CMVT patients were compared and analyzed. Binary logistic regression analyses were performed to identify potential risk factors of CMVT in patients with hip fractures. Finally we performed a receiver operating characteristic (ROC) curve analysis to compare the diagnostic values of different variables. RESULTS: The overall incidence of new-onset CMVT in patients with hip fractures was 18.75% (60 of 320). Among the 60 CMVT patients, 70% (42 of 60) were diagnosed with femoral neck fractures, 28.3% (17 of 60) with intertrochanteric fractures, and 1.7% (1 of 60) with subtrochanteric fractures. No pulmonary embolism (PE) occurred. High preoperative D-dimer (OR = 1.002, 95%CI 0.97-1.03), sex (OR = 1.22, 95%CI 0.51-2.96), the caprini score (OR = 2.32, 95%CI 1.05-5.16) and the waterlow score (OR = 1.077, 95%CI 0.35-3.36) significantly increased the risk of developing postoperative new-onset CMVT. CONCLUSIONS: CMVT has become a common clinical disease, and its harm should not be underestimated. Our study found that D-dimer, sex, the caprini score and the waterlow score were independent risk factors for postoperative CMVT. According to our clinical work, we should pay attention to identifying the risk factors of CMVT formation and targeted intervention measures to prevent new-onset CMVT.

Molecular basis and therapeutic potential of myostatin on bone formation and metabolism in orthopedic disease.

Myostatin, a member of the transforming growth factor-ß (TGF-ß) superfamily, is a key autocrine/paracrine inhibitor of skeletal muscle growth. Recently, researchers have postulated that myostatin is a negative regulator of bone formation and metabolism. Reportedly, myostatin is highly expressed in the fracture area, affecting the endochondral ossification process during the early stages of fracture healing. Furthermore, myostatin is highly expressed in the synovium of patients with rheumatoid arthritis (RA) and is an effective therapeutic target for interfering with osteoclast formation and joint destruction in RA. Thus, myostatin is a potent anti-osteogenic factor and a direct modulator of osteoclast differentiation. Evaluation of the molecular pathway revealed that myostatin can activate SMAD and mitogen-activated protein kinase signaling pathways, inhibiting the Wnt/ß-catenin pathway to synergistically regulate muscle and bone growth and metabolism. In summary, inhibition of myostatin or the myostatin signaling pathway has therapeutic potential in the treatment of orthopedic diseases. This review focused on the effects of myostatin on bone formation and metabolism and discussed the potential therapeutic effects of inhibiting myostatin and its pathways in related orthopedic diseases.

Expression and structural analysis of human neuroligin 2 and neuroligin 3 implicated in autism spectrum disorders.

The development of autism spectrum disorders (ASDs) involves both environmental factors such as maternal diabetes and genetic factors such as neuroligins (NLGNs). NLGN2 and NLGN3 are two members of NLGNs with distinct distributions and functions in synapse development and plasticity. The relationship between maternal diabetes and NLGNs, and the distinct working mechanisms of different NLGNs currently remain unclear. Here, we first analyzed the expression levels of NLGN2 and NLGN3 in a streptozotocin-induced ASD mouse model and different brain regions to reveal their differences and similarities. Then, cryogenic electron microscopy (cryo-EM) structures of human NLGN2 and NLGN3 were determined. The overall structures are similar to their homologs in previous reports. However, structural comparisons revealed the relative rotations of two protomers in the homodimers of NLGN2 and NLGN3. Taken together with the previously reported NLGN2-MDGA1 complex, we speculate that the distinct assembly adopted by NLGN2 and NLGN3 may affect their interactions with MDGAs. Our results provide structural insights into the potential distinct mechanisms of NLGN2 and NLGN3 implicated in the development of ASD.

Focusing on the hypoxia-inducible factor pathway: role, regulation, and therapy for osteoarthritis.

Osteoarthritis (OA) is a common chronic disabling disease that affects hundreds of millions of people around the world. The most important pathological feature is the rupture and loss of articular cartilage, and the characteristics of avascular joint tissues lead to limited repair ability. Currently, there is no effective treatment to prevent cartilage degeneration. Studies on the mechanism of cartilage metabolism revealed that hypoxia-inducible factors (HIFs) are key regulatory genes that maintain the balance of cartilage catabolism-matrix anabolism and are considered to be the major OA regulator and promising OA treatment target. Although the exact mechanism of HIFs in OA needs to be further clarified, many drugs that directly or indirectly act on HIF signaling pathways have been confirmed by animal experiments and regarded as promising treatments for OA. Targeting HIFs will provide a promising strategy for the development of new OA drugs. This article reviews the regulation of HIFs on intra-articular cartilage homeostasis and its influence on the progression of osteoarthritis and summarizes the recent advances in OA therapies targeting the HIF system.

Aerobic exercise-induced circulating extracellular vesicle combined decellularized dermal matrix hydrogel facilitates diabetic wound healing by promoting angiogenesis.

Background: Insufficient blood supply results in unsatisfactory wound healing, especially for challenging wound repair such as diabetic wound defects. Regular exercise training brings a lot of benefits to cardiovascular fitness and metabolic health including attenuation of T2DM progression. Circulating extracellular vesicles (EVs) are postulated to carry a variety of signals involved in tissue crosstalk by their modified cargoes, representing novel mechanisms for the effects of exercise. Prominently, both acute and chronic aerobic exercise training can promote the release of exercise-induced cytokines and enhance the angiogenic function of circulating angiogenic cell-derived EVs. Methods: We investigated the possible angiogenesis potential of aerobic exercise-induced circulating EVs (EXE-EVs) on diabetic wound healing. Circulating EVs were isolated from the plasma of rats subjected to 4 weeks of moderate aerobic exercise or sedentariness 24 h after the last training session. The therapeutic effect of circulating EVs was evaluated in vitro by proliferation, migration, and tube formation assays of human umbilical vein endothelial cells (HUVECs), as well as in vivo by quantification of angiogenesis and cutaneous wound healing in diabetic rats. Results: The number of circulating EVs did not change significantly in exercised rats 24 h post-exercise in comparison with the sedentary rats. Nevertheless, EXE-EVs showed remarkable pro-angiogenic effect by augmenting proliferation, migration, and tube formation of HUVECs. Furthermore, the findings of animal experiments revealed that the EXE-EVs delivered by decellularized dermal matrix hydrogel (DDMH) could significantly promote the repair of skin defects through stimulating the regeneration of vascularized skin. Discussion: The present study is the first attempt to demonstrate that aerobic exercise-induced circulating EVs could be utilized as a cell-free therapy to activate angiogenesis and promote diabetic wound healing. Our findings suggest that EXE-EVs may stand for a potential strategy for diabetic soft tissue wound repair.

Single-cell RNA-seq data analysis characterizing bronchoalveolar epithelial cells in patients with SARS-CoV-2 infection.

BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) has been reported to be the main receptor for SARS-CoV-2 infection of host cells. Understanding the changes in bronchoalveolar epithelial cells after SARS-CoV-2 infection of host cells and the intercellular communication relationship between these epithelial cell changes and immune cells is of great significance for the development of therapeutic methods. METHODS: We explored the single-cell RNA sequence (scRNA-seq) of cells infected with bronchoalveolar lavage fluid (BaLF) of patients with different severities of SARS-CoV-2 and healthy people. RESULTS: We found 11 clusters of epithelial cells in the BaLF, and they were derived from the S group. In the S group, the proportion of cells with positive ACE2 expression was relatively high. ACE2 was relatively more expressed in epithelial cell clusters 1, 3, and 7. Clusters 4 and 5 represented the original state, and there were two differentiation directions: one was cluster 2, and the others were clusters 1, 3, and 6. Cluster 7 was the intermediate state. Clusters 1, 3, 6, and 7 had high similarities (> 0.9), and their main signaling pathways focused on inflammatory activation and immune response. Cluster 2 was relatively specific and was up-regulated in differential genes that were mainly related to apoptosis. The ligand-receptor expression pattern of TNFRSF10D-TNFSF10 showed a special inter-cell regulatory relationship between epithelial cell cluster 2 and macrophages. CONCLUSION: This study revealed the changes in epithelial cells derived from alveolar lavage fluid after SARS-CoV-2 infection and the communication relationship with other immune cells.

Cryo-EM Structure and Activator Screening of Human Tryptophan Hydroxylase 2.

Human tryptophan hydroxylase 2 (TPH2) is the rate-limiting enzyme in the synthesis of serotonin. Its dysfunction has been implicated in various psychiatric disorders such as depression, autism, and bipolar disorder. TPH2 is typically decreased in stability and catalytic activity in patients; thus, screening of molecules capable of binding and stabilizing the structure of TPH2 in activated conformation is desired for drug development in mental disorder treatment. Here, we solved the 3.0 Å cryo-EM structure of the TPH2 tetramer. Then, based on the structure, we conducted allosteric site prediction and small-molecule activator screening to the obtained cavity. ZINC000068568685 was successfully selected as the best candidate with highest binding affinity. To better understand the driving forces and binding stability of the complex, we performed molecular dynamics simulation, which indicates that ZINC000068568685 has great potential to stabilize the folding of the TPH2 tetramer to facilitate its activity. The research might shed light on the development of novel drugs targeting TPH2 for the treatment of psychological disorders.