Spike substitution T813S increases Sarbecovirus fusogenicity by enhancing the usage of TMPRSS2.

SARS-CoV Spike (S) protein shares considerable homology with SARS-CoV-2 S, especially in the conserved S2 subunit (S2). S protein mediates coronavirus receptor binding and membrane fusion, and the latter activity can greatly influence coronavirus infection. We observed that SARS-CoV S is less effective in inducing membrane fusion compared with SARS-CoV-2 S. We identify that S813T mutation is sufficient in S2 interfering with the cleavage of SARS-CoV-2 S by TMPRSS2, reducing spike fusogenicity and pseudoparticle entry. Conversely, the mutation of T813S in SARS-CoV S increased fusion ability and viral replication. Our data suggested that residue 813 in the S was critical for the proteolytic activation, and the change from threonine to serine at 813 position might be an evolutionary feature adopted by SARS-2-related viruses. This finding deepened the understanding of Spike fusogenicity and could provide a new perspective for exploring Sarbecovirus' evolution.

CCDC50 promotes tumor growth through regulation of lysosome homeostasis.

The maintenance of lysosome homeostasis is crucial for cell growth. Lysosome-dependent degradation and metabolism sustain tumor cell survival. Here, we demonstrate that CCDC50 serves as a lysophagy receptor, promoting tumor progression and invasion by controlling lysosomal integrity and renewal. CCDC50 monitors lysosomal damage, recognizes galectin-3 and K63-linked polyubiquitination on damaged lysosomes, and specifically targets them for autophagy-dependent degradation. CCDC50 deficiency causes the accumulation of ruptured lysosomes, impaired autophagic flux, and superfluous reactive oxygen species, consequently leading to cell death and tumor suppression. CCDC50 expression is associated with malignancy, progression to metastasis, and poor overall survival in human melanoma. Targeting CCDC50 suppresses tumor growth and lung metastasis, and enhances the effect of BRAFV600E inhibition. Thus, we demonstrate critical roles of CCDC50-mediated clearance of damaged lysosomes in supporting tumor growth, hereby identifying a potential therapeutic target of melanoma.

Activation of STING by the novel liposomal TLC388 enhances the therapeutic response to anti-PD-1 antibodies in combination with radiotherapy.

Current immune checkpoint inhibiters (ICIs) have contrasting clinical results in poorly immunogenic cancers such as microsatellite-stable colorectal cancer (MSS-CRC). Therefore, understanding and developing the combinational therapeutics for ICI-unresponsive cancers is critical. Here, we demonstrated that the novel topoisomerase I inhibitor TLC388 can reshape the tumor immune landscape, corroborating their antitumor effects combined with radiotherapy as well as immunotherapy. We found that TLC388 significantly triggered cytosolic single-stranded DNA (ssDNA) accumulation for STING activation, leading to type I interferons (IFN-Is) production for increased cancer immunogenicity to enhance antitumor immunity. TLC388-treated tumors were infiltrated by a vast number of dendritic cells, immune cells, and costimulatory molecules, contributing to the favorable antitumor immune response within the tumor microenvironment. The infiltration of cytotoxic T and NK cells were more profoundly existed within tumors in combination with radiotherapy and ICIs, leading to superior therapeutic efficacy in poorly immunogenic MSS-CRC. Taken together, these results showed that the novel topoisomerase I inhibitor TLC388 increased cancer immunogenicity by ssDNA/STING-mediated IFN-I production, enhancing antitumor immunity for better therapeutic efficacy in combination with radiotherapy and ICIs for poorly immunogenic cancer.

Developmental validation of the STRSeqTyper122 kit for massively parallel sequencing of forensic STRs.

Massively parallel sequencing allows for integrated genotyping of different types of forensic markers, which reduces DNA consumption, simplifies experimental processes, and provides additional sequence-based genetic information. The STRseqTyper122 kit genotypes 63 autosomal STRs, 16 X-STRs, 42 Y-STRs, and the Amelogenin locus. Amplicon sizes of 117 loci were below 300 bp. In this study, MiSeq FGx sequencing metrics for STRseqTyper122 were presented. The genotyping accuracy of this kit was examined by comparing to certified genotypes of NIST standard reference materials and results from five capillary electrophoresis-based kits. The sensitivity of STRseqTyper122 reached 125 pg, and > 80% of the loci were correctly called with 62.5 pg and 31.25 pg input genomic DNA. Repeatability, species specificity, and tolerance for DNA degradation and PCR inhibitors of this kit were also evaluated. STRseqTyper122 demonstrated reliable performance with routine case-work samples and provided a powerful tool for forensic applications.

Mutasynthesis generates nine new pyrroindomycins.

Pyrroindomycins (PYRs) represent the only spirotetramate natural products discovered in nature, and possess potent activities against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. Their unique structure and impressive biological activities make them attractive targets for synthesis and biosynthesis; however, the discovery and generation of new PYRs remains challenging. To date, only the initial components A and B have been reported. Herein, we report a mutasynthesis approach for the generation of nine new PYRs with varying acyl modifications on their deoxy-trisaccharide moieties. This was achieved by blocking the formation of the acyl group 1,8-dihydropyrrolo[2,3-b]indole (DHPI) via gene pyrK1 inactivation and supplying chemical acyl precursors. The gene pyrK1 encodes a DUF1864 family protein that probably catalyzes the oxidative transformation of L-tryptophan to DHPI, and its deletion results in the abolishment of DHPI-containing PYRs and the accumulation of three new PYRs either without acyl modification or with DHPI replaced by benzoic acid and pyrrole-2-carboxylic acid. Capitalizing on the capacity of the ΔpyrK1 mutant to produce new PYRs, we have successfully developed a mutasynthesis strategy for the generation of six novel PYR analogs with various aromatic acid modifications on their deoxy-trisaccharide moieties, showcasing the potential for generating structurally diverse PYRs. Overall, this research contributes significantly to understanding the biosynthesis of PYRs and offers valuable perspectives on their structural diversity.

TRIM21 Ubiquitylates SQSTM1/p62 and Suppresses Protein Sequestration to Regulate Redox Homeostasis.

TRIM21 is a RING finger domain-containing ubiquitin E3 ligase whose expression is elevated in autoimmune disease. While TRIM21 plays an important role in immune activation during pathogen infection, little is known about its inherent cellular function. Here we show that TRIM21 plays an essential role in redox regulation by directly interacting with SQSTM1/p62 and ubiquitylating p62 at lysine 7 (K7) via K63-linkage. As p62 oligomerizes and sequesters client proteins in inclusions, the TRIM21-mediated p62 ubiquitylation abrogates p62 oligomerization and sequestration of proteins including Keap1, a negative regulator of antioxidant response. TRIM21-deficient cells display an enhanced antioxidant response and reduced cell death in response to oxidative stress. Genetic ablation of TRIM21 in mice confers protection from oxidative damages caused by arsenic-induced liver insult and pressure overload heart injury. Therefore, TRIM21 plays an essential role in p62-regulated redox homeostasis and may be a viable target for treating pathological conditions resulting from oxidative damage.

Nickel oxide nanoparticles: A new generation nanoparticles to combat bacteria Xanthomonas oryzae pv. oryzae and enhance rice plant growth.

Recently, nanotechnology is among the most promising technologies used in all areas of research. The production of metal nanoparticles using plant parts has received significant attention for its environmental friendliness and effectiveness. Therefore, we investigated the possible applications of biological synthesized nickel oxide nanoparticles (NiONPs). In this study, NiONPs were synthesized through biological method using an aqueous extract of saffron stigmas (Crocus sativus L). The structure, morphology, purity, and physicochemical properties of the obtained NPs were confirmed through Scanning/Transmission Electron Microscopy attached with Energy Dispersive Spectrum, X-ray Diffraction, and Fourier transform infrared. The spherically shaped NiONPs were found by Debye Scherer's formula to have a mean dimension of 41.19 nm. The application of NiONPs in vitro at 50, 100, and 200 µg/mL, respectively, produced a clear region of 2.0, 2.2, and 2.5 cm. Treatment of Xoo cell with NiONPs reduced the growth and biofilm formation, respectively, by 88.68% and 83.69% at 200 µg/mL. Adding 200 µg/mL NiONPs into Xoo cells produced a significant amount of ROS in comparison with the control. Bacterial apoptosis increased dramatically from 1.05% (control) to 99.80% (200 µg/mL NiONPs). When compared to the control, rice plants treated with 200 µg/mL NiONPs significantly improved growth characteristics and biomass. Interestingly, the proportion of diseased leaf area in infected plants with Xoo treated with NiONPs reduced to 22% from 74% in diseased plants. Taken together, NiONPs demonstrates its effectiveness as a promising tool as a nano-bactericide in managing bacterial infection caused by Xoo.

MMP-1 and MMP-9 are Highly Expressed in the Joint Capsule of Diabetic Frozen Shoulder.

BACKGROUND: The pathophysiology of frozen shoulder (FS) involves abnormal expressions of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) that lead capsular fibrosis. However, there has been little concern for why diabetic FS has more protracted fibrotic condition. The objective of this study was to compare the expression levels of MMPs and TIMPs in the joint capsule of patients with diabetic and non-diabetic FS. MATERIALS AND METHODS: Samples of capsular tissue were collected from 20 patients with FS (10 diabetic patients; diabetic group, and 10 non-diabetic patients; non-diabetic group) and 10 patients (control group) with chronic anterior shoulder instability. Quantitative real-time RT-PCR and Western blot analysis were performed to determine the expression levels of mRNA and protein for MMP-1, 3, 9, 13, 14, and TIMP-1, 2. RESULTS: The results of quantitative real-time RT-PCR showed significantly higher expression levels of all MMPs and TIMP-1 and significantly lower expression levels of TIMP-2 in the joint capsule of patients in the diabetic or non-diabetic groups compared with the control group. Significantly higher expression levels of MMP-1, 9, 14, and TIMP-1 were detected in the diabetic group compared with the non-diabetic group. The results of Western blot analysis showed significantly higher levels of MMP-3, 13, 14, and TIMP-1 in the joint capsule of patients in the diabetic or non-diabetic groups compared with the control group. However, no significant differences of protein levels of them were observed between diabetic and non-diabetic groups. CONCLUSIONS: The findings of this study demonstrate the potential involvement of MMP-1 and 9 in the pathophysiology of diabetic FS. These findings may be helpful in identification of therapeutic targets for development of novel treatments for this protracted chronic fibrosing condition.

Broadband and Spectrally Selective Photothermal Conversion through Nanocluster Assembly of Disordered Plasmonic Metasurfaces.

Plasmonic metasurfaces have been realized for efficient light absorption, thereby leading to photothermal conversion through nonradiative decay of plasmonic modes. However, current plasmonic metasurfaces suffer from inaccessible spectral ranges, costly and time-consuming nanolithographic top-down techniques for fabrication, and difficulty of scale-up. Here, we demonstrate a new type of disordered metasurface created by densely packing plasmonic nanoclusters of ultrasmall size on a planar optical cavity. The system either operates as a broadband absorber or offers a reconfigurable absorption band right across the visible region, resulting in continuous wavelength-tunable photothermal conversion. We further present a method to measure the temperature of plasmonic metasurfaces via surface-enhanced Raman spectroscopy (SERS), by incorporating single-walled carbon nanotubes (SWCNTs) as an SERS probe within the metasurfaces. Our disordered plasmonic system, generated by a bottom-up process, offers excellent performance and compatibility with efficient photothermal conversion. Moreover, it also provides a novel platform for various hot-electron and energy-harvesting functionalities.

F. Nucleatum enhances oral squamous cell carcinoma proliferation via E-cadherin/ß-Catenin pathway.

BACKGROUND: Fusobacterium nucleatum (F. nucleatum) is a microbial risk factor whose presence increases the risk of oral squamous cell carcinoma (OSCC) progression. However, whether it can promote the proliferation of OSCC cells remains unknown. METHODS: In this study, we investigated F. nucleatum effect on OSCC cell proliferation using in vitro and in vivo experiments. RESULTS: Our results showed that F. nucleatum promoted OSCC cell proliferation, doubling the cell count after 72 h (CCK-8 assay). Cell cycle analysis revealed G2/M phase arrest. F. nucleatum interaction with CDH1 triggered phosphorylation, upregulating downstream protein ß-catenin and activating cyclinD1 and Myc. Notably, F. nucleatum did not affect noncancerous cells, unrelated to CDH1 expression levels in CAL27 cells. Overexpression of phosphorylated CDH1 in 293T cells did not upregulate ß-catenin and cycle-related genes. In vivo BALB/c nude experiments showed increased tumor volume and Ki-67 proliferation index after F. nucleatum intervention. CONCLUSION: Our study suggests that F. nucleatum promotes OSCC cell proliferation through the CDH1/ß-catenin pathway, advancing our understanding of its role in OSCC progression and highlighting its potential as a therapeutic target.

Developmental validation of a high-resolution panel genotyping 639 Y-chromosome SNP and InDel markers and its evolutionary features in Chinese populations.

Uniparental-inherited haploid genetic marker of Y-chromosome single nucleotide polymorphisms (Y-SNP) have the power to provide a deep understanding of the human evolutionary past, forensic pedigree, and bio-geographical ancestry information. Several international cross-continental or regional Y-panels instead of Y-whole sequencing have recently been developed to promote Y-tools in forensic practice. However, panels based on next-generation sequencing (NGS) explicitly developed for Chinese populations are insufficient to represent the Chinese Y-chromosome genetic diversity and complex population structures, especially for Chinese-predominant haplogroup O. We developed and validated a 639-plex panel including 633 Y-SNPs and 6 Y-Insertion/deletions, which covered 573 Y haplogroups on the Y-DNA haplogroup tree. In this panel, subgroups from haplogroup O accounted for 64.4% of total inferable haplogroups. We reported the sequencing metrics of 354 libraries sequenced with this panel, with the average sequencing depth among 226 individuals being 3,741×. We illuminated the high level of concordance, accuracy, reproducibility, and specificity of the 639-plex panel and found that 610 loci were genotyped with as little as 0.03 ng of genomic DNA in the sensitivity test. 94.05% of the 639 loci were detectable in male-female mixed DNA samples with a mix ratio of 1:500. Nearly all of the loci were genotyped correctly when no more than 25 ng/µL tannic acid, 20 ng/µL humic acid, or 37.5 µM hematin was added to the amplification mixture. More than 80% of genotypes were obtained from degraded DNA samples with a degradation index of 11.76. Individuals from the same pedigree shared identical genotypes in 11 male pedigrees. Finally, we presented the complex evolutionary history of 183 northern Chinese Hans and six other Chinese populations, and found multiple founding lineages that contributed to the northern Han Chinese gene pool. The 639-plex panel proved an efficient tool for Chinese paternal studies and forensic applications.

Targeting CD73 increases therapeutic response to immunogenic chemotherapy by promoting dendritic cell maturation.

The CD39-CD73-adenosinergic pathway converts adenosine triphosphate (ATP) to adenosine for inhibiting anti-tumor immune responses. Therefore, targeting CD73 to reinvigorate anti-tumor immunity is considered the novel cancer immunotherapy to eradicate tumor cells. To fully understand the critical role of CD39/CD73 in colon adenocarcinoma (COAD), this study aims to comprehensive investigate the prognostic significance of CD39 and CD73 in stage I-IV COAD. Our data demonstrated that CD73 staining strongly marked malignant epithelial cells and CD39 was highly expressed in stromal cells. Attractively, tumor CD73 expression was significantly associated with tumor stage and the risk of distant metastasis, which suggested CD73 was as an independent factor for colon adenocarcinoma patients in univariate COX analysis [HR = 1.465, 95%CI = 1.084-1.978, p = 0.013]; however, high stromal CD39 in COAD patients was more likely to have favorable survival outcome [HR = 1.458, p = 1.103-1.927, p = 0.008]. Notably, high CD73 expression in COAD patients showed poor response to adjuvant chemotherapy and high risk of distant metastasis. High CD73 expression was inversely associated with less infiltration of CD45+ and CD8+ immune cells. However, administration with anti-CD73 antibodies significantly increased the response to oxaliplatin (OXP). Blockade of CD73 signaling synergistically enhanced OXP-induced ATP release, which is a marker of immunogenic cell death (ICD), promotes dendritic cell maturation and immune cell infiltration. Moreover, the risk of colorectal cancer lung metastasis was also decreased. Taken together, the present study revealed tumor CD73 expression inhibited the recruitment of immune cells and correlated with a poor prognosis in COAD patients, especially patients received adjuvant chemotherapy. Targeting CD73 to markedly increased the therapeutic response to chemotherapy and inhibited lung metastasis. Therefore, tumor CD73 may be an independent prognostic factor as well as the potential of therapeutic target for immunotherapy to benefit colon adenocarcinoma patients.

Opportunities and challenges of neoadjuvant targeted therapy in nonsmall cell lung cancer.

PURPOSE OF REVIEW: The aim of this study is to summarize the completed and ongoing clinical trials of neoadjuvant targeted therapy, discuss tolerability and efficacy, and explain the role of neoadjuvant targeted therapy in patients with resectable nonsmall cell lung cancer (NSCLC). At the same time, the existing challenges are presented, including assessment methods, biomarkers, surrogate endpoints and so on. We also put forward our views on possible ways to make improvements and establish neoadjuvant therapy a standard treatment in resectable NSCLC. RECENT FINDINGS: The mortality of lung cancer has decreased in the last 10 years, which can partly be attributed to advancement of targeted therapy. Targeted therapy has become the first-line treatment for patients with advanced mutation gene positive NSCLC, achieving the effect of prolonging overall survival (OS). Compared with chemotherapy, targeted therapy is associated with good tolerability and high response rate. Neoadjuvant targeted therapy has emerged in recent years and attracted attention of researchers. Early findings proved that neoadjuvant targeted therapy alone can improve patients' disease-free survival (DFS) and the efficacy of combining with other forms of neoadjuvant therapy is also being explored by researchers. SUMMARY: Neoadjuvant targeted therapy is playing an important role in NSCLC and worth more in-depth research.

Moiré Enhanced Potentials in Twisted Transition Metal Dichalcogenide Trilayers Homostructures.

The exploration of moiré superlatticesholds promising potential to uncover novel quantum phenomena emerging from the interplay of atomic structure and electronic correlation . However, the impact of the moiré potential modulation on the number of twisted layers has yet to be experimentally explored. Here, this work synthesizes a twisted WSe2 homotrilayer using a dry-transfer method and investigates the enhancement of the moiré potential with increasing number of twisted layers. The results of the study reveal the presence of multiple exciton resonances with positive or negative circularly polarized emission in the WSe2 homostructure with small twist angles, which are attributed to the excitonic ground and excited states confined to the moiré potential. The distinct g-factor observed in the magneto-optical spectroscopy is also shown to be a result of the confinement of the exciton in the moiré potential. The moiré potential depths of the twisted bilayer and trilayer homostructures are found to be 111 and 212 meV, respectively, an increase of 91% from the bilayer structure. These findings demonstrate that the depth of the moiré potential can be manipulated by adjusting the number of stacked layers, providing a promising avenue for exploration into highly correlated quantum phenomena.

PACT inhibits the replication of SARS-CoV-2 through the blockage of GSK-3ß-N-nsp3 cascade.

The protein activator of protein kinase R (PKR) (PACT) has been shown to play a crucial role in stimulating the host antiviral response through the activation of PKR, retinoic acid-inducible gene I, and melanoma differentiation-associated protein 5. Whether PACT can inhibit viral replication independent of known mechanisms is still unrevealed. In this study, we show that, like many viruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks GSK-3ß to facilitate its replication. GSK-3ß-induced phosphorylation on N protein increased the interaction between N protein and nsp3. Thus, GSK-3ß-N-nsp3 cascade promotes viral replication. Although SARS-CoV-2 can sabotage the activation of AKT, the upstream proteins suppressing the activation of GSK-3ß, we found that the host can use PACT, another protein kinase, instead of AKT to decrease the activity of GSK-3ß and the interaction between PACT and GSK-3ß is enhanced upon viral infection. Moreover, PACT inhibited the activity of GSK-3ß independent of its well-studied double-stranded RNA binding and PKR activating ability. In summary, this study identified an unknown function of PACT in inhibiting SARS-CoV-2 replication through the blockage of GSK-3ß-N-nsp3 cascade.

SARS-CoV-2 NSP7 inhibits type I and III IFN production by targeting the RIG-I/MDA5, TRIF, and STING signaling pathways.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a poor inducer of innate antiviral immunity, and the underlying mechanism still needs further investigation. Here, we reported that SARS-CoV-2 NSP7 inhibited the production of type I and III interferons (IFNs) by targeting the RIG-I/MDA5, Toll-like receptor (TLR3)-TRIF, and cGAS-STING signaling pathways. SARS-CoV-2 NSP7 suppressed the expression of IFNs and IFN-stimulated genes induced by poly (I:C) transfection and infection with Sendai virus or SARS-CoV-2 virus-like particles. NSP7 impaired type I and III IFN production activated by components of the cytosolic dsRNA-sensing pathway, including RIG-I, MDA5, and MAVS, but not TBK1, IKKε, and IRF3-5D, an active form of IRF3. In addition, NSP7 also suppressed TRIF- and STING-induced IFN responses. Mechanistically, NSP7 associated with RIG-I and MDA5 prevented the formation of the RIG-I/MDA5-MAVS signalosome and interacted with TRIF and STING to inhibit TRIF-TBK1 and STING-TBK1 complex formation, thus reducing the subsequent IRF3 phosphorylation and nuclear translocation that are essential for IFN induction. In addition, ectopic expression of NSP7 impeded innate immune activation and facilitated virus replication. Taken together, SARS-CoV-2 NSP7 dampens type I and III IFN responses via disruption of the signal transduction of the RIG-I/MDA5-MAVS, TLR3-TRIF, and cGAS-STING signaling pathways, thus providing novel insights into the interactions between SARS-CoV-2 and innate antiviral immunity.

Microwave ablation versus laparoscopic resection as first-line therapy for solitary 3-5-cm HCC.

BACKGROUND AND AIMS: The study objective was to compare the effectiveness of microwave ablation (MWA) and laparoscopic liver resection (LLR) on solitary 3-5-cm HCC over time. APPROACH AND RESULTS: From 2008 to 2019, 1289 patients from 12 hospitals were enrolled in this retrospective study. Diagnosis of all lesions were based on histopathology. Propensity score matching was used to balance all baseline variables between the two groups in 2008-2019 (n = 335 in each group) and 2014-2019 (n = 257 in each group) cohorts, respectively. For cohort 2008-2019, during a median follow-up of 35.8 months, there were no differences in overall survival (OS) between MWA and LLR (HR: 0.88, 95% CI 0.65-1.19, p = 0.420), and MWA was inferior to LLR regarding disease-free survival (DFS) (HR 1.36, 95% CI 1.05-1.75, p = 0.017). For cohort 2014-2019, there was comparable OS (HR 0.85, 95% CI 0.56-1.30, p = 0.460) and approached statistical significance for DFS (HR 1.33, 95% CI 0.98-1.82, p = 0.071) between MWA and LLR. Subgroup analyses showed comparable OS in 3.1-4.0-cm HCCs (HR 0.88, 95% CI 0.53-1.47, p = 0.630) and 4.1-5.0-cm HCCs (HR 0.77, 95% CI 0.37-1.60, p = 0.483) between two modalities. For both cohorts, MWA shared comparable major complications (both p > 0.05), shorter hospitalization, and lower cost to LLR (all p < 0.001). CONCLUSIONS: MWA might be a first-line alternative to LLR for solitary 3-5-cm HCC in selected patients with technical advances, especially for patients unsuitable for LLR.

Strain-tunable valley polarization and localized excitons in monolayer WSe2.

Monolayer transition metal dichalcogenides (TMDs) have a crystalline structure with broken spatial inversion symmetry, making them promising candidates for valleytronic applications. However, the degree of valley polarization is usually not high due to the presence of intervalley scattering. Here, we use the nanoindentation technique to fabricate strained structures of WSe2 on Au arrays, thus demonstrating the generation and detection of strained localized excitons in monolayer WSe2. Enhanced emission of strain-localized excitons was observed as two sharp photoluminescence (PL) peaks measured using low-temperature PL spectroscopy. We attribute these emerging sharp peaks to excitons trapped in potential wells formed by local strains. Furthermore, the valley polarization of monolayer WSe2 is modulated by a magnetic field, and the valley polarization of strained localized excitons is increased, with a high value of up to approximately 79.6%. Our results show that tunable valley polarization and localized excitons can be realized in WSe2 monolayers, which may be useful for valleytronic applications.

Celsr2 regulates NMDA receptors and dendritic homeostasis in dorsal CA1 to enable social memory.

Social recognition and memory are critical for survival. The hippocampus serves as a central neural substrate underlying the dynamic coding and transmission of social information. Yet the molecular mechanisms regulating social memory integrity in hippocampus remain unelucidated. Here we report unexpected roles of Celsr2, an atypical cadherin, in regulating hippocampal synaptic plasticity and social memory in mice. Celsr2-deficient mice exhibited defective social memory, with rather intact levels of sociability. In vivo fiber photometry recordings disclosed decreased neural activity of dorsal CA1 pyramidal neuron in Celsr2 mutants performing social memory task. Celsr2 deficiency led to selective impairment in NMDAR but not AMPAR-mediated synaptic transmission, and to neuronal hypoactivity in dorsal CA1. Those activity changes were accompanied with exuberant apical dendrites and immaturity of spines of CA1 pyramidal neurons. Strikingly, knockdown of Celsr2 in adult hippocampus recapitulated the behavioral and cellular changes observed in knockout mice. Restoring NMDAR transmission or CA1 neuronal activities rescued social memory deficits. Collectively, these results show a critical role of Celsr2 in orchestrating dorsal hippocampal NMDAR function, dendritic and spine homeostasis, and social memory in adulthood.

Laser-Textured Hybrid Brass Pattern Array Surface for High-Efficiency Fog Collection.

Fog collection holds promise for addressing water shortage. However, the conventional fabrication of fog collection devices, normally chemical methods, suffers many challenges, such as complicated preparation and environmental issues. Herein, we proposed a green fabrication strategy to construct superhydrophobic/hydrophilic surfaces on the brass substrate via the combination of laser fabrication and heat treatment. The wettability of brass is directly dictated by the laser process parameters. The different superhydrophobic/hydrophilic hybrid pattern surface with a rectangular/triangular array was designed for an optimal fog collection performance. The maximum water collection efficiency of the prepared surface is measured up to 427.36 mg h-1 cm-2, which is 97% higher than that of the control sample. Furthermore, the surface can be folded into different forms to realize a flexible collector. We envision that our work provides a green fabrication strategy to construct a superwetting surface for highly efficient fog collection.