18F-FDG PET/CT image of NK/T cell lymphoma in the sacroiliac joint.

NK/T cell lymphoma in the sacroiliac joint is very rare. We reportfluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) findings of NK/T cell lymphoma in the sacroiliac joint in a 48-year-old man. On 18F-FDG PET/CT image, it manifested a soft tissue mass with adjacent bone destruction in the sacroiliac joint, which had intense 18F-FDG uptake. The final pathology supported a diagnosis of NK/T cell lymphoma. Our case added the knowledge of another rare site of NK/T cell lymphoma, which should be regarded as a differential diagnosis for sacroiliac joint mass with intense 18F-FDG uptake.

Identification of mutations in viral proteins involved in cell adaptation using a reverse genetic system of the live attenuated hepatitis A virus vaccine H2 strain.

The live attenuated hepatitis A virus vaccine H2 strain was developed by passaging a wild- type H2w isolate in cell cultures. Currently, the mechanism underlying its attenuation phenotype remain largely unknown. In this study, we generated a full-length infectious cDNA clone of the H2 strain using in-fusion techniques. The recovered H2 strain (H2ic) from the cDNA clone exhibited an efficient replication in both the hepatoma cell line Huh7.5.1 and the 2BS cell line used for vaccine production, similar to the parental H2 strain. Additionally, H2ic did not cause disease in Ifnar1-/- C57 mice, consistent with the H2 strain. To explore the cell-adaptive mutations of the H2 strain, chimeric viruses were generated by replacing its non-structural proteins with corresponding regions from H2w using the infectious cDNA clone as a genetic backbone. The chimeric viruses carrying the 3C or 3D proteins from H2w showed decreased replication in Huh7.5.1 and 2BS cell lines compared to H2ic. Other chimeric viruses containing the 2B, 2C, or 3A proteins from H2w failed to be recovered. Furthermore, there were no significant differences in disease manifestation in mice between H2ic and the recovered chimeric viruses. These results demonstrate that adaptive mutations in the 2B, 2C, and 3A proteins are essential for efficient replication of the H2 strain in cell cultures. Mutations in the 3C and 3D proteins contribute to enhanced replication in cell cultures but did not influence the attenuated phenotypes in mice. Together, this study presents the first reverse genetic system of the H2 strain and identifies viral proteins essential for adaptation to cell cultures.

Reaction Characteristics of Calcination and Decomposition of Phosphogypsum in a Bubbling Fluidized Bed.

A bubbling fluidized bed reactor is designed to investigate the high-temperature calcination and decomposition characteristics of phosphogypsum (PG). The reactor employs electric heating, and a lifting discharge tube is installed in the middle of the air distributor to allow flexible switching between batch and continuous feeding modes. The batch test results show that the solid-phase bed materials with a PG particle size of 0.27-0.55 mm and a coal particle size of 0.55-0.83 mm are found to have uniformly mixed at a PG/coal mass ratio of 5:1 and calcined at a high temperature of 1100 °C for 30 min. PG completely decomposes to yield mainly CaS and a small amount of Ca2(SiO4) as the solid-phase products. For the above-mentioned optimal process parameters, a 120 min thermal-state continuous test is conducted. Feeding and discharging are performed at intervals of 30 min to maintain the stability of the static bed height inside the reactor. The results indicate that the PG decomposition rate is higher than 92% in the batch and continuous tests. However, the continuous decomposition of PG has significant process advantages, such as a higher CaS yield (71.20%) compared to that in the batch mode (64.49%). Furthermore, PG undergoes agglomeration and bonding within the particles when heated, intensifying the formation of a Ca2(SiO4) eutectic.

Processing causal structure sentences in Mandarin Chinese: an eye movements study.

It remains uncertain whether causal structure prediction can improve comprehension in Chinese sentences and whether the position of the headword mediates the prediction effect. We conducted an experiment to explore the effect of causal prediction and headword position in Chinese sentence reading. Participants were asked to read sentences containing causal connectives with their eye movements recorded. In the experiment, we manipulated the causal structure of the sentence and the position of the headword. We found a promoting effect of causal structure on first-pass reading time and a hindering impact on total reading time. However, the effect was not mediated by the headword position. The results show that causal syntactic prediction facilitated early-stage processing and increased the integration cost in the late stage of Chinese sentence processing. These findings also support the constraint-based approach, which suggests an isolation between semantic and syntactic processing.

Characteristics of T-Cell Receptor Repertoire for Differential Response to Methotrexate Treatment for Rheumatoid Arthritis.

BACKGROUND: Methotrexate (MTX) serves as the initial treatment for rheumatoid arthritis (RA). However, a substantial proportion of RA patients, estimated between 30% and 50%, do not respond positively to MTX. While the T-cell receptor (TCR) is crucial for the immune response during RA, its role in differentiating MTX responsiveness has not been thoroughly investigated. METHODS: This study used next-generation sequencing to analyze the TCR ß-chain complementary determining region sequences in peripheral blood mononuclear cells obtained from RA patients before MTX treatment. This study aimed to compare the characteristics of the TCR repertoire between the MTX responder and non-responder groups. RESULTS: The study identified a significant difference in the TRBV6-6 gene (p = .003) concerning MTX treatment response. Additionally, a significant difference was found in the number of "3" nucleotide deletions at the 5'Jdels site (p = .023) in the VDJ rearrangement. CONCLUSION: These findings suggest distinct TCR repertoire characteristics between MTX responder and non-responder groups among RA patients. This discovery offers new insights into understanding the variable responses of RA patients to MTX therapy.

Screening and identification of reactive metabolic compounds of Cortex Periplocae based on glutathione capture-mass spectrometry.

As a traditional Chinese medicine (TCM), Cortex Periplocae (CP) has a wide range of pharmacological effects, as well as toxic side effects. The main toxic components of it are cardiac glycosides, which tend to cause cardiotoxicity. Currently, it has also been reported in studies to cause hepatotoxicity, but it is not clear whether the hepatotoxicity is related to the toxicity caused by the reactive metabolites. This study aims to investigate the target components of CP that generate reactive metabolic toxicity. The fluorescent probe method was used to detect glutathione (GSH)-trapped reactive metabolites in a co-incubation system of CP extract with rat liver microsomes. Identification of GSH conjugates was performed by LC-MS/MS and that of the possible precursor components that produce reactive metabolites was conducted by UPLC-Q-TOF/MS. Cell viability assays were performed on HepG2 and L02 cells to determine the cytotoxicity of the target components. The findings of our study demonstrate that the extract derived from CP has the ability to generate metabolites that exhaust the intracellular GSH levels, resulting in the formation of GSH conjugates and subsequent cytotoxic effects. Through the utilization of the UPLC-Q-TOF/MS technique, we were able to accurately determine the molecular weight of the precursor compound in CP to be 355.1023. The primary evidence to determining the GSH conjugetes relies on the appearance of characteristic product ions resulting from central neutral loss (CNL) scanning of 129 Da and product scanning of m/z 660 in the positive MS/MS spectrum. Through analysis, it was ultimately ascertained that the presence of chlorogenic acid (CGA) and its isomers, namely neochlorogenic acid (NCGA) and cryptochlorogenic acid (CCGA), could lead to the production of GSH conjugates, resulting in cytotoxicity at elevated levels. Taking these findings into consideration, the underlying cause for the potential hepatotoxicity of CP was initially determined.

Covalent adaptable polymer networks with CO2-facilitated recyclability.

Cross-linked polymers with covalent adaptable networks (CANs) can be reprocessed under external stimuli owing to the exchangeability of dynamic covalent bonds. Optimization of reprocessing conditions is critical since increasing the reprocessing temperature costs more energy and even deteriorates the materials, while reducing the reprocessing temperature via molecular design usually narrows the service temperature range. Exploiting CO2 gas as an external trigger for lowering the reprocessing barrier shows great promise in low sample contamination and environmental friendliness. Herein, we develop a type of CANs incorporated with ionic clusters that achieve CO2-facilitated recyclability without sacrificing performance. The presence of CO2 can facilitate the rearrangement of ionic clusters, thus promoting the exchange of dynamic bonds. The effective stress relaxation and network rearrangement enable the system with rapid recycling under CO2 while retaining excellent mechanical performance in working conditions. This work opens avenues to design recyclable polymer materials with tunable dynamics and responsive recyclability.

Differentiating low-risk thymomas from high-risk thymomas: preoperative radiomics nomogram based on contrast enhanced CT to minimize unnecessary invasive thoracotomy.

BACKGROUND: This study was designed to develop a combined radiomics nomogram to preoperatively predict the risk categorization of thymomas based on contrast-enhanced computed tomography (CE-CT) images. MATERIALS: The clinical and CT data of 178 patients with thymoma (100 patients with low-risk thymomas and 78 patients with high-risk thymomas) collected in our hospital from March 2018 to July 2023 were retrospectively analyzed. The patients were randomly divided into a training set (n = 125) and a validation set (n = 53) in a 7:3 ratio. Qualitative radiological features were recorded, including (a) tumor diameter, (b) location, (c) shape, (d) capsule integrity, (e) calcification, (f) necrosis, (g) fatty infiltration, (h) lymphadenopathy, and (i) enhanced CT value. Radiomics features were extracted from each CE-CT volume of interest (VOI), and the least absolute shrinkage and selection operator (LASSO) algorithm was performed to select the optimal discriminative ones. A combined radiomics nomogram was further established based on the clinical factors and radiomics scores. The differentiating efficacy was determined using receiver operating characteristic (ROC) analysis. RESULTS: Only one clinical factor (incomplete capsule) and seven radiomics features were found to be independent predictors and were used to establish the radiomics nomogram. In differentiating low-risk thymomas (types A, AB, and B1) from high-risk ones (types B2 and B3), the nomogram demonstrated better diagnostic efficacy than any single model, with the respective area under the curve (AUC), accuracy, sensitivity, and specificity of 0.974, 0.921, 0.962 and 0.900 in the training cohort, 0.960, 0.892, 0923 and 0.897 in the validation cohort, respectively. The calibration curve showed good agreement between the prediction probability and actual clinical findings. CONCLUSIONS: The nomogram incorporating clinical factors and radiomics features provides additional value in differentiating the risk categorization of thymomas, which could potentially be useful in clinical practice for planning personalized treatment strategies.

Exosomal miR-486 derived from bone marrow mesenchymal stem cells promotes angiogenesis following cerebral ischemic injury by regulating the PTEN/Akt pathway.

Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) have been shown to promote angiogenesis after ischemic stroke, in which microRNAs (miRs) are believed to play an important role in exosome-mediated therapeutic effects, though the mechanism is still not clear. In this study, a series of molecular biological and cellular assays, both in vitro and in vivo, were performed to elucidate the role of exosomal miR-486 in angiogenesis following cerebral ischemic and its molecular mechanisms. Our results revealed that BMSC-Exos significantly improved neurological function and increased microvessel density in ischemic stroke rats. In vitro assays showed that BMSC-Exos promoted the proliferation, migration, and tube formation ability of oxygen-glucose deprivation/reoxygenation (OGD/R) injured rat brain microvascular endothelial cells (RBMECs). Importantly, BMSC-Exos increased the expression of miR-486 and phosphorylated protein kinase B (p-Akt) and down-regulated the protein level of phosphatase and tensin homolog (PTEN) in vivo and in vitro. Mechanistic studies demonstrated that transfection with miR-486 mimic enhanced RBMECs angiogenesis and increased p-Akt expression, while inhibited PTEN expression. On the other hand, the miR-486 inhibitor induced an opposite effect, which could be blocked by PTEN siRNA. It was thus concluded that exosomal miR-486 from BMSCs may enhance the functional recovery by promoting angiogenesis following cerebral ischemic injury, which might be related to its regulation of the PTEN/Akt pathway.

DNA Origami-Constructed Nanotapes for Sunitinib Adsorption and Inhibition of Renal Clear Carcinoma Cells.

Sunitinib (SUN) is a first-line drug for the treatment of renal clear carcinoma cells by targeting receptor tyrosine kinases (RTK) on the cell membrane. However, the effective delivery of SUN to the cell membrane remains a significant challenge. In this study, we fabricated precisely structured DNA nanotapes with strong surface SUN adhesion, enabling RTK inhibition of renal clear carcinoma cells. In our design, the precisely assembled linear topological six-helical-bundle DNA origami serves as the framework, and positively charged chitosan is adsorbed onto the DNA origami surface, thereby forming DNA nanotapes. The SUN was efficiently loaded onto the surface of the DNA nanotapes by electrostatic interaction. We found that DNA nanotapes exhibit excellent stability in serum. Importantly, DNA nanotapes carrying SUN can achieve prolonged cell membrane retention and inhibit RTK, thereby enhancing cytotoxicity toward 786-0 cells. Taken together, this study provides a promising candidate platform for the efficient delivery of cell membrane receptor inhibitors in anticancer therapy.

DNA methylation profiling deciphers three EMT subtypes with distinct prognoses and therapeutic vulnerabilities in breast cancer.

Background: Epithelial-mesenchymal transition (EMT), deemed a pivotal hallmark of tumours, is intricately regulated by DNA methylation and encompasses multiple states along tumour progression. The potential mechanisms that drive the intrinsic heterogeneity of breast cancer (BC) via EMT transformation have not been identified, presenting a significant obstacle in clinical diagnosis and treatment. Methods: A total of 7,602 patients have been included in this study. We leveraged integrated multiomics data (epigenomic, genomic, and transcriptomic data) to delineate the comprehensive landscape of EMT in BC. Subsequently, a subtyping classifier was developed through a machine learning framework proposed by us. Results: We classified the BC samples into three methylation-driven EMT subtypes with distinct features, namely, C1 (the mammary duct development subtype with TP53 activation), C2 (the immune infiltration subtype with high TP53 mutation), and C3 (the ERBB2 amplification subtype with an unfavorable prognosis). Specifically, patients with the C1 subtype might respond to endocrine therapy or the p53-MDM2 antagonist nutlin-3. Patients with the C2 subtype might benefit from combined therapeutic regimens involving radiotherapy, PARP inhibitors, and immune checkpoint blockade therapy. Patients with the C3 subtype might benefit from anti-HER2 agents such as lapatinib. Notably, to increase the clinical applicability of the EMT subtypes, we devised a 96-gene panel-based classifier via a machine learning framework. Conclusions: Our study identified three methylation-driven EMT subtypes with distinct prognoses and biological traits to capture heterogeneity in BC and provided a rationale for the use of this classification as a powerful tool for developing new strategies for clinical trials.

Shallow groundwater table fluctuations weaken nitrogen accumulation in the thin layer vadose zone of cropland around plateau lakes, Southwest China.

Excessive accumulation of nitrogen (N) in the soil profile in the intensive agricultural region will seriously threaten groundwater quality and safety. However, the impact of shallow groundwater table (SGWT) fluctuations driven by seasonal variations on the N accumulation characterizations in the soil profiles has not been well quantified, particularly in the regions with thin layer vadose zone. Through in-situ monitoring and simulation experiments, the changes in the SGWT and N accumulation of soil profile in intensive cropland around 7 plateau lakes in Yunnan were studied during the rainy season (RS) and dry season (DS), and the N loss in soil profile of cropland driven by SGWT fluctuations was estimated. The results showed that the SGWT and N accumulation in soil profile of cropland around the plateau lakes had obvious seasonal variation characteristics. The proportion of N storage in different forms in 60-100 cm soil layer in the RS was greater than that in the DS, particularly the proportion of NH4+-N storage was as high as 55 %, while N accumulation in surface soil was obvious in the DS. Compared with the DS, due to the rising SGWT in the RS, the maximum storages of TN and NO3--N in the 0-100 cm soil layer decreased by17% and 36 %, respectively. The TN loss intensities from the 0-100 cm soil profiles of cropland around Fuxian Lake, Yilong Lake, Qilu Lake, Dianchi Lake, Yangzong Lake, Erhai Lake, and Xingyun Lake were 74, 54, 127, 105, 93, 72 and 207 kg/ha, respectively. Moreover, if the SGWT was <30 cm, the average TN loss intensity and amount could reach 177 kg/ha and 1250 t, respectively. Therefore, the SGWT regulation was one of the key measures to reducing soil N loss from the thin layer vadose zone of cropland around plateau lakes and improving groundwater quality.

High-Throughput Screening and Prediction of Nucleophilicity of Amines Using Machine Learning and DFT Calculations.

Nucleophilic index (NNu) as a significant parameter plays a crucial role in screening of amine catalysts. Indeed, the quantity and variety of amines are extensive. However, only limited amines exhibit an NNu value exceeding 4.0 eV, rendering them potential nucleophiles in chemical reactions. To address this issue, we proposed a computational method to quickly identify amines with high NNu values by using Machine Learning (ML) and high-throughput Density Functional Theory (DFT) calculations. Our approach commenced by training ML models and the exploration of Molecular Fingerprint methods as well as the development of quantitative structure-activity relationship (QSAR) models for the well-known amines based on NNu values derived from DFT calculations. Utilizing explainable Shapley Additive Explanation plots, we were able to determine the five critical substructures that significantly impact the NNu values of amine. The aforementioned conclusion can be applied to produce and cultivate 4920 novel hypothetical amines with high NNu values. The QSAR models were employed to predict the NNu values of 259 well-known and 4920 hypothetical amines, resulting in the identification of five novel hypothetical amines with exceptional NNu values (>4.55 eV). The enhanced NNu values of these novel amines were validated by DFT calculations. One novel hypothetical amine, H1, exhibits an unprecedentedly high NNu value of 5.36 eV, surpassing the maximum value (5.35 eV) observed in well-established amines. Our research strategy efficiently accelerates the discovery of the high nucleophilicity of amines using ML predictions, as well as the DFT calculations.

Conventional ultrasonography enabled with augmented reality needle guidance for percutaneous kidney access: An innovative methodologies randomized controlled trial.

IMPORTANCE: Successful needle puncture of the renal collecting system is a critical but difficult procedure in percutaneous nephrolithotomy (PCNL). Although fluoroscopy and ultrasound are the standard imaging techniques to guide puncture during PCNL, both have known limitations. OBJECTIVE: To assess the feasibility and safety of a new navigation system for needle puncture in ultrasound-guided PCNL. DESIGN: This study employed a single-center randomized controlled trial (RCT) design to assess the feasibility and safety of a new navigation system for needle puncture in ultrasound-guided PCNL. Conducted between May 2021 and November 2021, the trial utilized computer-generated random numbers for participant allocation to control for selection bias. SETTING: The trial was executed at the *********, which serves as an academic medical center. PARTICIPANTS: All patients who met the inclusion criteria were randomly divided into two groups, with 29 patients in each group. One group underwent PCNL procedures using the new navigation system, while the control group underwent standard ultrasound-guided PCNL procedures. Included patients had renal pelvis or caliceal calculi larger than 2.0 cm in diameter or had multiple or staghorn stones. The puncture procedure was performed with the support of real-time ultrasound imaging and visual guidance displayed on the screen. MAIN OUTCOMES AND MEASURES: The primary outcome was system feasibility and puncture success rate. Secondary outcomes included puncture time, total surgical time, number of attempts, post-procedure complications, and one-year and three-year stone recurrence rates. Stone clearance was defined by postoperative CT. Descriptive statistics summarized patient demographics, stone size, and location. Independent samples t-tests analyzed puncture time and total surgical time. Chi-square or Fisher's exact tests compared stone clearance, complications, socioeconomic status, renal hydronephrosis, stone location, race, and medical history. Linear regression examined the correlation between BMI and puncture time. Significance was set at P<0.05. RESULTS: For all 58 patients undergoing PCNL, needle punctures of the renal collecting system were completed with a success rate of 100%. The average time from planning the puncture protocol to successful puncture was significantly shorter in the AcuSee guidance system group (3.12 min, range 0.2-6.88 min) compared to the standard ultrasound-guided group (7.58 min, range 5.41-10.68 min), representing a reduction of approximately 59%. The total surgical time was also shorter in the AcuSee group for patients with no and mild hydronephrosis (P<0.05). Complication rates were lower in the AcuSee group, with no major complications observed. However, 3 patients in the standard ultrasound-guided group have adverse effects after the PCNL procedure. The one-year stone recurrence rate was significantly lower in the AcuSee group (3.4%) compared to the standard group (24.1%), and the three-year recurrence rate was also lower (6.9% vs. 41.4%). Patient-specific factors such as BMI, renal morphology, and prior surgical history did not significantly affect the performance of the AcuSee system. CONCLUSIONS AND RELEVANCE: We report the first clinical application of a new navigation system for needle puncture in ultrasound-guided PCNL. It has been demonstrated that it is feasible and safe compared to the standard ultrasound-guided group in percutaneous renal puncture. This technology provides intuitive and easy-to-use visual guidance, which may facilitate safe, accurate and fast needle puncture of the kidney.

Hyperhomocysteine promotes cataract development through mTOR-mediated inhibition of autophagy and connexins expression.

AIM: Hyperhomocysteine has been recognized as an independent risk factor of multiple diseases, including several eye diseases. In this study, we aim to investigate whether increased homocysteine (Hcy) is related to cataracts, and to explore whether dysregulation of mTOR-mediated autophagy and connexin expression are underlying mechanisms. METHOD: We first developed a method of liquid chromatography tandem mass spectrometry to accurately measure serum concentrations of Hcy in 287 cataract patients and 334 healthy controls. Next, we treated human lens epithelial (HLC-B3) cells with Hcy at different concentrations and durations, and then analyzed expression of autophagy-related markers and connexins, as well as phosphorylated mTOR (p-mTOR) in these cells by Western blotting. Formation of autophagic vacuoles and intracellular Ca2+ in the Hcy-treated cells were observed by fluorescence microscopy. Further, we performed a rescue experiment in the Hcy-treated HLC-B3 cells by pre-incubation with rapamycin, an mTOR inhibitor. RESULTS: The serum levels of Hcy in patients with cataracts were significantly increased compared to those in healthy controls. In cultured HLC-B3 cells, expression of autophagy related markers (LC3B and Beclin1) and connexins (Cx43 and Cx50) was inhibited by Hcy treatment in a dose- and duration-dependent manner. Accumulation of Ca2+ in the Hcy-treated lens epithelial cells was observed as a consequence of reduced connexin expression. Meanwhile, expression of p-mTOR increased, representing up-regulation of the mTOR pathway. Importantly, inhibition of autophagy and connexin expression due to hyperhomocysteine was rescued via mTOR suppression by pretreatment with rapamycin in HLC-B3 cells. CONCLUSION: Our results demonstrate that hyperhomocysteine might promote cataract development through two mTOR-mediated pathways in the lens epithelial cells: 1) dysregulation of autophagy and 2) accumulation of intracellular calcium via decreased connexin expression.

A ratiometric fluorescent probe for selective detection of hypochlorite (ClO-) and gallium (III) (Ga3+) ions in environmental and food samples.

Hypochlorite (ClO-) and gallium (Ⅲ) ions (Ga3+) have extensive applications in various human industries and daily activities. However, their inherent toxicity poses significant risks to environmental preservation and human well-being. Hence, the development of reliable and handy detection tools for ClO- and Ga3+ in the environment and food is crucial. In this study, a ratiometric fluorescent probe was prepared based on benzothiazolaldehyde and pyridine-2-carboxylic acid hydrazide, which exhibited exceptional performance characteristics for the selective detection of ClO- and Ga3+. These features include high specificity, low detection limits (0.28 µM for ClO-, 0.13 µM for Ga3+), mild pH conditions (pH 4-11 for ClO-, pH 6-11 for Ga3+), fast response time (within 30 s), as well as versatile applicability across different matrices such as water, soil, food, and plant samples. Additionally, this probe can be used with a smartphone color recognition app. The probe offers a convenient and effective tool for the detection of ClO- and Ga3+, demonstrating its potential application value in environmental monitoring and food safety.

Phonon Directionality Impacts Electron-Phonon Coupling and Polarization of the Band-Edge Emission in Two-Dimensional Metal Halide Perovskites.

Two-dimensional metal halide perovskites are highly versatile for light-driven applications due to their exceptional variety in material composition, which can be exploited for the tunability of mechanical and optoelectronic properties. The band-edge emission is defined by the structure and composition of both organic and inorganic layers, and electron-phonon coupling plays a crucial role in the recombination dynamics. However, the nature of the electron-phonon coupling and what kind of phonons are involved are still under debate. Here we investigate the emission, reflectance, and phonon response from single two-dimensional lead iodide microcrystals with angle-resolved polarized spectroscopy. We find an intricate dependence of the emission polarization with the vibrational directionality in the materials, which reveals that several bands of low-frequency phonons with nonorthogonal directionality contribute to the band-edge emission. Such complex electron-phonon coupling requires adequate models to predict the thermal broadening of the emission and provides opportunities to design polarization properties.

Structural insights into the Caprin-2 HR1 domain in canonical Wnt signaling.

The canonical Wnt signaling pathway plays crucial roles in cell fate decisions as well as in pathogenesis of various diseases. Previously, we reported Caprin-2 as a new regulator of canonical Wnt signaling through a mechanism of facilitating LRP5/6 phosphorylation. Here, we resolved the crystal structure of the N-terminal homologous region 1 (HR1) domain of human Caprin-2 (hCap2_HR1). HR1 domain is so far only observed in Caprin-2 and its homologous protein Caprin-1, and the function of this domain remains largely mysterious. Here, the structure showed that hCap2_HR1 forms a homo-dimer and exhibits an overall structure roughly resembling the appearance of a pair of scissors. Moreover, we found that residues R200 and R201, which located at a basic cluster within the N-terminal "blades" region, are critical for Caprin-2's localization to the plasma membrane. In line with this, mutations targeting these two residues decrease Caprin-2's activity in the canonical Wnt signaling. Overall, we characterized a previously unknown "scissors"-like structure of the full-length HR1 domain, and revealed its function in mediating Caprin-2's localization to the plasma membrane.

Double Perovskite Interlayer Stabilized Highly Efficient Perovskite Solar Cells.

Metal halide perovskite solar cell (PSC) technology has an impressive power conversion efficiency (PCE) exceeding 26.1% and demonstrates cost-effective manufacturing. However, the stability of these PSCs poses a significant challenge, hindering their widespread manufacturing and commercialization. To tackle the degradation issue inherent in PSCs, surface passivation techniques, particularly employing a thin layer of two-dimensional (2D) perovskites, create a 2D/3D heterostructure. Beyond this, the exploration of metal halide double perovskites adds a new dimension to the chemical and band gap phase space of materials for optoelectronic applications. In this study, we leverage a wide band gap double perovskite interlayer to enhance the stability of 3D metal halide perovskite. Specifically, the double perovskite nanoparticle Cs2AgBiBr6, with its substantial band gap of 2.2 eV and exceptional air stability, is utilized. Through optimization, a Cs2AgBiBr6-treated PSC achieves an open-circuit voltage of 1.12 V and an impressive PCE of 19.52%. Additionally, the Cs2AgBiBr6 passivation layer proves to be effective in bolstering the stability of PSCs. This work demonstrates an additional strategy and design motif to simultaneously increase the PCE of PSCs along with achieving improved stability.

Phenotyping of FGF12AV52H mutation in mouse implies a complex FGF12 network.

Pathogenic missense mutation of the FGF12 gene is responsible for a variable disease phenotypic spectrum. Disease-specific therapies require precise dissection of the relationship between different mutations and phenotypes. The lack of a proper animal model hinders the investigation of related diseases, such as early-onset epileptic encephalopathy. Here, an FGF12AV52H mouse model was generated using CRISPR/Cas9 technology, which altered the A isoform without affecting the B isoform. The FGF12AV52H mice exhibited seizure susceptibility, while no spontaneous seizures were observed. The increased excitability in dorsal hippocampal CA3 neurons was confirmed by patch-clamp recordings. Furthermore, immunostaining showed that the balance of excitatory/inhibitory neurons in the hippocampus of the FGF12AV52H mice was perturbed. The increases in inhibitory SOM+ neurons and excitatory CaMKII+ neurons were heterogeneous. Moreover, the locomotion, anxiety levels, risk assessment behavior, social behavior, and cognition of the FGF12AV52H mice were investigated by elevated plus maze, open field, three-chamber sociability, and novel object tests, respectively. Cognition deficit, impaired risk assessment, and social behavior with normal social indexes were observed, implying complex consequences of V52H FGF12A in mice. Together, these data suggest that the function of FGF12A in neurons can be immediate or long-term and involves modulation of ion channels and the differentiation and maturation of neurons. The FGF12AV52H mouse model increases the understanding of the function of FGF12A, and it is of great importance for revealing the complex network of the FGF12 gene in physiological and pathological processes.