FACS-based genome-wide CRISPR screens define key regulators of DNA damage signaling pathways.

DNA damage-activated signaling pathways are critical for coordinating multiple cellular processes, which must be tightly regulated to maintain genome stability. To provide a comprehensive and unbiased perspective of DNA damage response (DDR) signaling pathways, we performed 30 fluorescence-activated cell sorting (FACS)-based genome-wide CRISPR screens in human cell lines with antibodies recognizing distinct endogenous DNA damage signaling proteins to identify critical regulators involved in DDR. We discovered that proteasome-mediated processing is an early and prerequisite event for cells to trigger camptothecin- and etoposide-induced DDR signaling. Furthermore, we identified PRMT1 and PRMT5 as modulators that regulate ATM protein level. Moreover, we discovered that GNB1L is a key regulator of DDR signaling via its role as a co-chaperone specifically regulating PIKK proteins. Collectively, these screens offer a rich resource for further investigation of DDR, which may provide insight into strategies of targeting these DDR pathways to improve therapeutic outcomes.

A machine learning enhanced EMS mutagenesis probability map for efficient identification of causal mutations in Caenorhabditis elegans.

Chemical mutagenesis-driven forward genetic screens are pivotal in unveiling gene functions, yet identifying causal mutations behind phenotypes remains laborious, hindering their high-throughput application. Here, we reveal a non-uniform mutation rate caused by Ethyl Methane Sulfonate (EMS) mutagenesis in the C. elegans genome, indicating that mutation frequency is influenced by proximate sequence context and chromatin status. Leveraging these factors, we developed a machine learning enhanced pipeline to create a comprehensive EMS mutagenesis probability map for the C. elegans genome. This map operates on the principle that causative mutations are enriched in genetic screens targeting specific phenotypes among random mutations. Applying this map to Whole Genome Sequencing (WGS) data of genetic suppressors that rescue a C. elegans ciliary kinesin mutant, we successfully pinpointed causal mutations without generating recombinant inbred lines. This method can be adapted in other species, offering a scalable approach for identifying causal genes and revitalizing the effectiveness of forward genetic screens.

In vivo CRISPR screens identify Mga as an immunotherapy target in triple-negative breast cancer.

Immune evasion is not only critical for tumor initiation and progression, but also determines the efficacy of immunotherapies. Through iterative in vivo CRISPR screens with seven syngeneic tumor models, we identified core and context-dependent immune evasion pathways across cancer types. This valuable high-confidence dataset is available for the further understanding of tumor intrinsic immunomodulators, which may lead to the discovery of effective anticancer therapeutic targets. With a focus on triple-negative breast cancer (TNBC), we found that Mga knock-out significantly enhances antitumor immunity and inhibits tumor growth. Transcriptomics and single-cell RNA sequencing analyses revealed that Mga influences various immune-related pathways in the tumor microenvironment. Our findings suggest that Mga may play a role in modulating the tumor immune landscape, though the precise mechanisms require further investigation. Interestingly, we observed that low MGA expression in breast cancer patients correlates with a favorable prognosis, particularly in those with active interferon-γ signaling. These observations provide insights into tumor immune escape mechanisms and suggest that further exploration of MGA's function could potentially lead to effective therapeutic strategies in TNBC.

Integrated screens uncover a cell surface tumor suppressor gene KIRREL involved in Hippo pathway.

Cell surface proteins play essential roles in various biological processes and are highly related to cancer development. They also serve as important markers for cell identity and targets for pharmacological intervention. Despite their great potentials in biomedical research, comprehensive functional analysis of cell surface proteins remains scarce. Here, with a de novo designed library targeting cell surface proteins, we performed in vivo CRISPR screens to evaluate the effects of cell surface proteins on tumor survival and proliferation. We found that Kirrel1 loss markedly promoted tumor growth in vivo. Moreover, KIRREL was significantly enriched in a separate CRISPR screen based on a specific Hippo pathway reporter. Further studies revealed that KIRREL binds directly to SAV1 to activate the Hippo tumor suppressor pathway. Together, our integrated screens reveal a cell surface tumor suppressor involved in the Hippo pathway and highlight the potential of these approaches in biomedical research.

The transmembrane and cytosolic domains of equine herpesvirus type 1 glycoprotein D determine Golgi retention by regulating vesicle formation.

Accumulating evidence underscores the pivotal role of envelope proteins in viral secondary envelopment. However, the intricate molecular mechanisms governing this phenomenon remain elusive. To shed light on these mechanisms, we investigated a Golgi-retained gD of EHV-1 (gDEHV-1), distinguishing it from its counterparts in Herpes Simplex Virus-1 (HSV-1) and Pseudorabies Virus (PRV). To unravel the specific sequences responsible for the Golgi retention phenotype, we employed a gene truncation and replacement strategy. The results suggested that Golgi retention signals in gDEHV-1 exhibiting a multi-domain character. The extracellular domain of gDEHV-1 was identified as an endoplasmic reticulum (ER)-resident domain, the transmembrane domain and cytoplasmic tail (TM-CT) of gDEHV-1 were integral in facilitating the protein's residence within the Golgi complex. Deletion or replacement of either of these dual domains consistently resulted in the mutant gDEHV-1 being retained in an ER-like structure. Moreover, (TM-CT)EHV-1 demonstrated a preference for binding to endomembranes, inducing the generation of a substantial number of vesicles, potentially originate from the Golgi complex or the ER-Golgi intermediate compartment. In conclusion, our findings provide insights into the intricate molecular mechanisms governing the Golgi retention of gDEHV-1, facilitating the comprehension of the processes underlying viral secondary envelopment.

A novel protein FNDC3B-267aa encoded by circ0003692 inhibits gastric cancer metastasis via promoting proteasomal degradation of c-Myc.

BACKGROUND: Gastric cancer (GC) ranks fifth in global cancer incidence and third in mortality rate among all cancer types. Circular RNAs (circRNAs) have been extensively demonstrated to regulate multiple malignant biological behaviors in GC. Emerging evidence suggests that several circRNAs derived from FNDC3B play pivotal roles in cancer. However, the role of circFNDC3B in GC remains elusive. METHODS: We initially screened circFNDC3B with translation potential via bioinformatics algorithm prediction. Subsequently, Sanger sequencing, qRT-PCR, RNase R, RNA-FISH and nuclear-cytoplasmic fractionation assays were explored to assess the identification and localization of circ0003692, a circRNA derived from FNDC3B. qRT-PCR and ISH were performed to quantify expression of circ0003692 in human GC tissues and adjacent normal tissues. The protein-encoding ability of circ0003692 was investigated through dual-luciferase reporter assay and LC/MS. The biological behavior of circ0003692 in GC was confirmed via in vivo and in vitro experiments. Additionally, Co-IP and rescue experiments were performed to elucidate the interaction between the encoded protein and c-Myc. RESULTS: We found that circ0003692 was significantly downregulated in GC tissues. Circ0003692 had the potential to encode a novel protein FNDC3B-267aa, which was downregulated in GC cells. We verified that FNDC3B-267aa, rather than circ0003692, inhibited GC migration in vitro and in vivo. Mechanistically, FNDC3B-267aa directly interacted with c-Myc and promoted proteasomal degradation of c-Myc, resulting in the downregulation of c-Myc-Snail/Slug axis. CONCLUSIONS: Our study revealed that the novel protein FNDC3B-267aa encoded by circ0003692 suppressed GC metastasis through binding to c-Myc and enhancing proteasome-mediated degradation of c-Myc. The study offers the potential applications of circ0003692 or FNDC3B-267aa as therapeutic targets for GC.

Ag-modified enhance the performances of ZnO@CFs based omnidirectional photoelectrochemical ultraviolet detectors.

There are several prospective applications for omnidirectional ultraviolet (UV) detectors and underwater detection detectors in optical systems and optical fields. In this work, ZnO nanorods arrays were grown on carbon fibers (CFs). An appropriate amount of Ag nanoparticles (NPs) was deposited on the surface of ZnO nanorods by photochemical deposition. This improved the performance of photoelectrochemical (PEC) based UV detectors. Under 365 nm and 10 mW cm-2UV irradiation, the photocurrent density of the 30s-Ag/ZnO@CFs based PEC UV detector can reach 1.28 mA cm-2, which is about 7 times that of the ZnO@CFs based PEC UV detector, and the rising time is shortened from 0.17 to 0.10 s. The reason is that increased absorption of ultraviolet light induced by the localized surface plasmon resonance. In addition, the detector exhibits a good flexibility and remains flexible after hundreds of bends and twists. Moreover, the detector is responsive in the range of rotation angle from 0° to 360°. It provides an insight to improve the photoelectric performance and underwater omnidirectional detection ability of the PEC UV detector.

PTBP1 knockdown impairs autophagy flux and inhibits gastric cancer progression through TXNIP-mediated oxidative stress.

BACKGROUND: Gastric cancer (GC) is a prevalent malignant tumor, and the RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1) has been identified as a crucial factor in various tumor types. Moreover, abnormal autophagy levels have been shown to significantly impact tumorigenesis and progression. Despite this, the precise regulatory mechanism of PTBP1 in autophagy regulation in GC remains poorly understood. METHODS: To assess the expression of PTBP1 in GC, we employed a comprehensive approach utilizing western blot, real-time quantitative polymerase chain reaction (RT-qPCR), and bioinformatics analysis. To further identify the downstream target genes that bind to PTBP1 in GC cells, we utilized RNA immunoprecipitation coupled with sequencing (si-PTBP1 RNA-seq). To evaluate the impact of PTBP1 on gastric carcinogenesis, we conducted CCK-8 assays, colony formation assays, and GC xenograft mouse model assays. Additionally, we utilized a transmission electron microscope, immunofluorescence, flow cytometry, western blot, RT-qPCR, and GC xenograft mouse model experiments to elucidate the specific mechanism underlying PTBP1's regulation of autophagy in GC. RESULTS: Our findings indicated that PTBP1 was significantly overexpressed in GC tissues compared with adjacent normal tissues. Silencing PTBP1 resulted in abnormal accumulation of autophagosomes, thereby inhibiting GC cell viability both in vitro and in vivo. Mechanistically, interference with PTBP1 promoted the stability of thioredoxin-interacting protein (TXNIP) mRNA, leading to increased TXNIP-mediated oxidative stress. Consequently, this impaired lysosomal function, ultimately resulting in blockage of autophagic flux. Furthermore, our results suggested that interference with PTBP1 enhanced the antitumor effects of chloroquine, both in vitro and in vivo. CONCLUSION: PTBP1 knockdown impairs GC progression by directly binding to TXNIP mRNA and promoting its expression. Based on these results, PTBP1 emerges as a promising therapeutic target for GC.

Effect of storage temperature on the dimensional stability of DLP printed casts.

STATEMENT OF PROBLEM: Despite studies focusing on the accuracy and dimensional stability of additive manufacturing, research on the impact of storage conditions on these properties of 3-dimensional (3D) printed objects is lacking. PURPOSE: The purpose of this in vitro study was to investigate the influence of storage temperature on the dimensional stability of digital light processing (DLP) printed casts and to determine how different locations in printed casts react differently. MATERIAL AND METHODS: A completely dentate maxillary typodont model was digitized with a desktop laser scanner. The typodont was subsequently modified with a software program by adding cuboids with a side length of 3 mm on both maxillary central incisors, first molars, and second molars. The file was saved in the standard tessellation language (STL) format. The modified digitized typodont was then processed through the DLP technology printing process with a desktop DLP printer and photopolymerizing resin. The casts were printed 32 times and stored in sealed plastic bags, shielded from light, and subjected to 4 different temperature conditions (-20 °C, 4 °C, 20 °C, and 37 °C, n=8 each). The cuboids on the central incisors were labeled as the P1 group, first molars as the P2 group, and second molars as the P3 group. The distance between the cuboids was measured 5 times, with results recorded immediately after cast production and at 1, 2, 3, 5, 7, 14, and 28 days after. Repeated analysis of variance (ANOVA) and the Tukey honestly significant difference (HSD) test were used to compare the recorded values among the groups (α=.05). RESULTS: In the P1 group, the casts stored at -20 °C exhibited the smallest overall size change, with a mean ±standard deviation volume of 99.42 ±0.04% compared with the original casts after 28 days of storage. This was followed by the casts stored at 4 °C, 20 °C, and 37 °C, with remaining volumes of 99.39 ±0.06% (P=.139), 99.14 ±0.08% (P<.001), and 98.96 ±0.03% (P<.001), respectively. For the P2 and P3 groups, casts stored at 4 °C retained the most volume at 99.82 ±0.01%, whereas those stored at -20 °C, 20 °C, and 37 °C underwent greater changes, with remaining volumes of 99.66 ±0.03%, 100.32 ±0.02%, and 100.44 ±0.02%, respectively (P<.001). The P3 group exhibited a similar trend to that of the P2 group, with the casts stored at 4 °C remaining closest to the original dimensions at 99.86 ±0.02%, while casts stored at -20 °C showed 99.73 ±0.03% of the original volume and those stored at 20 °C and 37 °C expanded with volumes of 100.37 ±0.03% and 100.48 ±0.03%, respectively (P<.001). CONCLUSIONS: DLP printed casts stored at 4 °C exhibited the greatest overall dimensional stability, followed sequentially by those stored at -20 °C, 20 °C, and 37 °C. Additionally, the study confirmed that the posterior and anterior teeth regions of DLP printed casts respond differently to different storage temperatures.

A fully digital workflow to design anterior guidance for an implant-supported single crown using a modified patient-specific motion technique.

Current methods for designing anterior guidance of anterior fixed prostheses are either complicated or lack accuracy. The article describes a fully digital workflow to design individualized anterior guidance of an implant-supported single crown by using a modified patient-specific motion technique. The technique aims to optimize the digital occlusal design workflow, thereby improving the occlusal fit and long-term stability of anterior fixed prostheses.

[Trueness of different digital design methods for incisal guidance of maxillary anterior implant-supported single crowns].

OBJECTIVE: To compare the trueness of incisal guidance of implant-supported single crowns designed by patient-specific motion (PSM) with that designed by average-value virtual articulator (AVA). METHODS: The study had recruited 12 participants with complete dentition and stable incisal guidance. An intraoral scanner was used to scan digital casts and record two types of patient-specific motion (data only including protrusive movement, and data including protrusive movement and lateral protrusive movement). The lingual surfaces of the maxillary incisors which guided the protrusive movement was selected and elevated to create a reference cast. A maxillary central incisor of original casts was vir-tually extracted and implanted to generate a working cast. The Dental system software program was used to design implant-supported single crowns with the anatomical coping design method. The incisal guidance was designed by different methods. The incisal guidance in control group was designed by the average-value virtual articulator. The incisal guidance in experiment groups was designed by the patient-specific motion only including protrusive movement (PSM1) and with the patient-specific motion including protrusive movement and lateral protrusive movement (PSM2). The incisal guidance of prosthesis designed by these 3 methods were compared with the original incisal guidance in Geomagic Control 2015 (3DSystem, America). The measurements included: Average of positive values, ratio of positive area and maximum value reflecting supra-occlusion; average of negative values, ratio of negative area and minimum value reflecting over-correction; and root mean square reflecting overall deviation. RESULTS: Statistical data were collected using the median (interquartile range) method. The average of positive values, ratio of positive area and average of negative values of the PSM2 group were smaller than those of the control group [8.0 (18.8) µm vs. 37.5 (47.5) µm; 0 vs. 7.2% (38.1%); -109.0 (63.8) µm vs.-66.5 (64.5) µm], and the ratio of negative area of PSM2 group was larger than those of the control group [52.9% (47.8%) vs. 17.3% (45.3%)], with significant differences (P all < 0.05). The ratio of positive area [0.1% (7.0%)] and average of negative values [-97.0 (61.5) µm] of PSM1 group, were smaller than those of the control group, and the ratio of negative area [40.7% (39.2%)] of the PSM1 group was larger than that of the control group, with significant differences (P < 0.05). The average of positive values [20.0 (42.0) µm] and ratio of positive area of PSM1 group was larger than that of the PSM2 group with significant differences (P < 0.05). CONCLUSION: To establish the incisor guidance of implant-supported single crowns, compared with the average-value virtual articulator and the patient-specific motion only including protrusive movement, the patient-specific motion including protrusive movement and lateral protrusive movement is more conducive to reducing the protrusive interference of prosthesis and improving the occlusal fit.

CircNFATC3 promotes the proliferation of gastric cancer through binding to IGF2BP3 and restricting its ubiquitination to enhance CCND1 mRNA stability.

BACKGROUND: Insulin like growth factor II mRNA binding protein 3 (IGF2BP3) is an RNA binding protein with multiple roles in regulation of gene expression at the post-transcriptional level and is implicated in tumorigenesis and progression of numerous cancers including gastric cancer (GC). Circular RNAs (circRNAs) are a diverse endogenous noncoding RNA population that have important regulatory roles in cancer. However, circRNAs that regulate the expression of IGF2BP3 in GC is largely unknown. METHODS: CircRNAs that bound to IGF2BP3 were screened in GC cells using RNA immunoprecipitation and sequencing (RIP-seq). The identification and localization of circular nuclear factor of activated T cells 3 (circNFATC3) were identified using Sanger sequencing, RNase R assays, qRT-PCR, nuclear-cytoplasmic fractionation and RNA-FISH assays. CircNFATC3 expression in human GC tissues and adjacent normal tissues were measured by qRT-PCR and ISH. The biological role of circNFATC3 in GC was confirmed by in vivo and in vitro experiments. Furthermore, RIP, RNA-FISH/IF, IP and rescue experiments were performed to uncover interactions between circNFATC3, IGF2BP3 and cyclin D1 (CCND1). RESULTS: We identified a GC-associated circRNA, circNFATC3, that interacted with IGF2BP3. CircNFATC3 was significantly overexpressed in GC tissues and was positively associated with tumor volume. Functionally, the proliferation of GC cells decreased significantly after circNFATC3 knockdown in vivo and in vitro. Mechanistically, circNFATC3 bound to IGF2BP3 in the cytoplasm, which enhanced the stability of IGF2BP3 by preventing ubiquitin E3 ligase TRIM25-mediated ubiquitination, thereby enhancing the regulatory axis of IGF2BP3-CCND1 and promoting CCND1 mRNA stability. CONCLUSIONS: Our findings demonstrate that circNFATC3 promotes GC proliferation by stabilizing IGF2BP3 protein to enhance CCND1 mRNA stability. Therefore, circNFATC3 is a potential novel target for the treatment of GC.

Effect of a novel interocclusal recording method on occlusal accuracy of implant-supported fixed prostheses: A randomized clinical trial.

OBJECTIVES: To investigate the effect of a novel interocclusal recording method on the occlusal accuracy of implant-supported fixed prostheses for partially dentate patients with distal extension. MATERIALS AND METHODS: Twenty patients with two or more adjacent teeth missing in the distal extension and scheduled to receive implant-supported fixed prostheses were enrolled. Two interocclusal recording methods were used: placing polyvinyl siloxane (PVS) on the interocclusal recording caps (test), and placing PVS on healing abutments (control). The intraoral occlusal contacts in maximal intercuspal position (MIP) were compared with those in the mounted casts to calculate sensitivity and positive predictive value (PPV). Then, patients were randomly allocated into two groups to determine which interocclusal record would be used. The implant prostheses' evaluations mainly included occlusal adjustment height, volume, and time, occlusal contact score based on articulating paper examination. Paired-samples t-test, Mann-Whitney U test, and least squares regression analyzed the statistic differences. RESULTS: The test method had higher sensitivity to detect intraoral occlusal contacts than the control method (p = .002), but similar PPV (p = .10). During the prostheses' evaluations, the occlusal adjustment height in the test group was significantly lower than that in the control group [99.4 (53.2, 134.2) vs. 159.0 (82.3, 247.8) µm, p = .03], while the occlusal contact score before adjustment was higher (p = .006). The groups had similar occlusal adjustment volume and time. CONCLUSIONS: The novel interocclusal recording method for implant-supported fixed prostheses was more accurate and could reduce the occlusal adjustment.

Comparison of the dimensional and morphological accuracy of three-dimensional digital dental casts digitized using different methods.

The purpose of this study was to compare the accuracy of digital dental casts from plaster cast scanning (PCS), impression scanning (IPS), intraoral scanning (IOS), and cone-beam computed tomography (CBCT) scanning (CCS) methods. The maxillary and mandibular dental casts of 15 patients who needed CBCT scans for oral examination or treatment were digitized via four methods. 12 linear distance measurements of all digital dental casts were selected and acquired with software and compared to those of the reference plaster cast to evaluate the dimensional accuracy. Three-dimensional deviation analysis of the IPS, IOS and CCS groups with respect to the reference PCS group was performed to evaluate the morphological accuracy. The discrepancy in linear distances between the digital dental casts and reference plaster casts was statistically significant (p < 0.01). The dimensional accuracies of the PCS (0.06 ± 0.12 mm) and IPS (0.03 ± 0.05 mm) casts were better than those of the IOS (0.37 ± 0.30 mm) and CCS (0.54 ± 0.40 mm) casts. The one-sample t test showed that there were statistically significant differences between the discrepancies in 8 of the linear distances for the PCS group and 9 of the linear distances for the IPS group between the digital dental casts and reference plaster casts, with an ideal error of 0.00 (p < 0.05). The sequence of morphological accuracy from good to poor was maxillary and mandibular IPS, mandibular IOS; maxillary IOS; and maxillary and mandibular CCS. The accuracy of the digital dental casts from the PCS and IPS methods was greater than that of IOS and CCS methods. Although accuracy of the digital dental cast from IOS was low, it satisfied the clinical requirements for fixed restorations in small units. The accuracy of the digital dental cast from CCS was poorest and could only be used for procedures with lower accuracy requirements.

A technique to fabricate a custom CAD-CAM periapical radiographic film holder for implant assessment.

Standardized radiographs produced by using the paralleling technique play an important role in monitoring prosthetic misfit and marginal bone levels around endosseous implants. Under clinical conditions, parallel adjustment of the film with respect to the implant requires the use of positioning devices. This article describes the fabrication of a custom computer-aided design and computer-aided manufacturing (CAD-CAM) device suitable for implants adjacent to natural teeth.

Digitally designed occlusion of an implant-supported crown considering physiological tooth displacement under occlusal loading.

Physiological natural tooth displacement under occlusal loading can influence intraoral occlusal contacts. However, gypsum casts and digital scans cannot simulate the physiological tooth displacement under occlusal loading. The occlusal design of the implant-supported crowns has been based mainly on the experience of dental laboratory technicians, lacking accuracy and individualization. Therefore, a digital technique that considers physiological tooth displacement is presented to design the occlusion of implant-supported single crowns.

Preliminary application and evaluation of digital step-by-step tooth-preparation templates.

STATEMENT OF PROBLEM: Tooth preparation is a fundamental technique, and inaccurate preparation may lead to excessive irreversible tooth removal or insufficient restorative space. The conventional process depends mostly on operator experience, and variable quality is inevitable. Whether a tooth preparation template would be beneficial, especially for inexperienced dentists, is unclear. PURPOSE: The purpose of this preliminary study was to evaluate the application of new digitally designed step-by-step templates to guide tooth preparation. MATERIAL AND METHODS: A laboratory scanner was used to obtain digital scans of dental casts. A 3-dimensional reverse engineering software program was used for the step-by-step digital design. The data for a series of guide templates were imported into a computer-aided manufacturing (CAM) machine for milling. Ten experts and 10 inexperienced dentists prepared teeth on a dentoform in a mannequin head. They were instructed to complete the preparation within 20 minutes both with and without the step-by-step template. The prepared crowns were subsequently scanned with an intraoral scanner, the scans were imported into a preparation evaluation software program, and various indexes were scored. The t test was used to analyze the differences between the 2 methods of tooth preparation in each group (α=.05). RESULTS: No significant differences were found in total scores with and without the guide templates in the expert group (P=.256), but the scores in the inexperienced group differed significantly between the 2 preparation methods (P<.001). In undercut comparisons, the 2 methods of preparation did not differ significantly in the expert (P=.912) or inexperienced groups (P=.601). However, the scores for taper and occlusal reduction were significantly higher in the inexperienced group when using the guide template (P<.001). CONCLUSIONS: The new digitally designed step-by-step tooth preparation guide template significantly improved the efficiency and quality of tooth preparation for inexperienced dentists when preparing multiple teeth.

One-Step Calcination Synthesis of Bulk-Doped Surface-Modified Ni-Rich Cathodes with Superlattice for Long-Cycling Li-Ion Batteries.

Nickel-rich (Ni≥90 %) layered cathodes are critical materials for achieving higher-energy-density and lower-cost next-generation Li-ion batteries (LIBs). However, their bulk and interface structural instabilities significantly impair their electrochemical performance, thus hindering their widespread adoption in commercial LIBs. Exploiting Ti and Mo diffusion chemistry, we report one-step calcination to synthesize bulk-to-surface modified LiNi0.9 Co0.09 Mo0.01 O2 (NCMo90) featuring a 5 nm Li2 TiO3 coating on the surface, a Mo-rich Li+ /Ni2+ superlattice at the sub-surface, and Ti-doping in the bulk. Such a multi-functional structure effectively maintains its structural integrity upon cycling. As a result, such NCMo90 exhibits a high initial capacity of 221 mAh g-1 at 0.1 C, excellent rate performance (184 mAh g-1 at 5 C), and high capacity retention of 94.0 % after 500 cycles. This work opens a new avenue to developing industry-applicable Ni-rich cathodes for next-generation LIBs.

Effects of hCG on DA neuronal death of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, with the incidence in men being about twice as compared to women. Gender differences may provide clues for finding key targets that mediate the death of dopaminergic (DA) neurons in PD. Luteinizing hormone (LH), analog of human chorionic gonadotropin (hCG), and their receptor, luteinizing hormone/choriogonadotropin receptor (LHCGR), are associated with the pathogenesis of PD. Movement-related symptoms are partially improved by hCG in PD patients. However, the relationship between hCG and PD, as well as its roles in mediating DA neuronal death, has not been elucidated. In this study, we investigated the potential of hCG as a treatment during PD progression. After establishment of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse models, we found that hCG restored the decrease of LHCGR activity caused by down-regulation of LH in the substantia nigra. Furthermore, the reduction of LHCGR activity led to DA neuronal death through knocking down the LHCGR in DA neurons by AAV-mTH-shRNA. Treatment with hCG alleviated the DA neuronal death induced by MPTP. Finally, hCG exerted neuroprotective effects by inhibiting the activation of glycogen synthase kinase 3 beta (GSK3ß) in our MPTP-induced PD mouse and MPP+-treated SH-SY5Y cell models. Together, these results demonstrate that hCG exerts neuroprotective effects for PD through LHCGR, and the inhibition of GSK3ß activation is involved in this protective effect, suggesting that hCG can be taken as a potential therapeutic for the treatment of PD.

Chemi-Mechanically Peeling the Unstable Surface States of α-FAPbI3.

Surface states are one of the crucial factors determining the phase stability of formamidinium-based perovskites. Compared with other compositions, exclusive lattice strain in FAPbI3 perovskite generates defects at the surface more readily, making them more vulnerable at the surface and easier to trigger the phase transition from α-phase to the non-perovskite δ-phase. In order to regulate the surface quality, here, a chemi-mechanical cleavage approach is reported, i.e., tape peel-zone (PZ), implemented by attaching and peeling off the ordinary Kapton Tapes. The PZ approach can simultaneously eliminate the surface defects of perovskite and siliconize the film surface with hydrophobic silicone compounds. These two functionalities endow α-FAPbI3 perovskite with a robust hydrophobic surface, which can sustain for 30 days under a relative humidity of 60% and withstand the high temperature up to 240 °C. The unencapsulated PZ-treated cells show 80.3% of initial performance after 90 h of continuous operation in ambient air, which is 31.4 times more stable than the pristine cell.