Publisher Correction: ANKRD16 prevents neuron loss caused by an editing-defective tRNA synthetase.

In the Fig. 3b western blot of this Article, 'Myc-AlaRS' in row one should have been 'Myc-AAD Aars', 'AlaRS' in row two should have been 'Aars' and 'ANKRD16' in row four should have been 'Ankrd16'. In Fig. 4f, 'ANKRD16' and 'ANKRD16(3xR)' should have been 'Ankrd16' and 'Ankrd163xR; and in Fig. 3c the position of the molecular mass markers had shifted. These figures have been corrected online, and see Supplementary Information to the accompanying Amendment for the original figure.

ANKRD16 prevents neuron loss caused by an editing-defective tRNA synthetase.

Editing domains of aminoacyl tRNA synthetases correct tRNA charging errors to maintain translational fidelity. A mutation in the editing domain of alanyl tRNA synthetase (AlaRS) in Aars sti mutant mice results in an increase in the production of serine-mischarged tRNAAla and the degeneration of cerebellar Purkinje cells. Here, using positional cloning, we identified Ankrd16, a gene that acts epistatically with the Aars sti mutation to attenuate neurodegeneration. ANKRD16, a vertebrate-specific protein that contains ankyrin repeats, binds directly to the catalytic domain of AlaRS. Serine that is misactivated by AlaRS is captured by the lysine side chains of ANKRD16, which prevents the charging of serine adenylates to tRNAAla and precludes serine misincorporation in nascent peptides. The deletion of Ankrd16 in the brains of Aarssti/sti mice causes widespread protein aggregation and neuron loss. These results identify an amino-acid-accepting co-regulator of tRNA synthetase editing as a new layer of the machinery that is essential to the prevention of severe pathologies that arise from defects in editing.

DJ-1 Molecular Chaperone Activity Depresses Tau Aggregation Propensity through Interaction with Monomers.

Tau aggregate-bearing lesions are pathological markers and potential mediators of tauopathic neurodegenerative diseases, including Alzheimer's disease. The molecular chaperone DJ-1 colocalizes with tau pathology in these disorders, but it has been unclear what functional link exists between them. In this study, we examined the consequences of tau/DJ-1 interaction as isolated proteins in vitro. When added to full-length 2N4R tau under aggregation-promoting conditions, DJ-1 inhibited both the rate and extent of filament formation in a concentration-dependent manner. Inhibitory activity was low affinity, did not require ATP, and was not affected by substituting oxidation incompetent missense mutation C106A for wild-type DJ-1. In contrast, missense mutations previously linked to familial Parkinson's disease and loss of α-synuclein chaperone activity, M26I and E64D, displayed diminished tau chaperone activity relative to wild-type DJ-1. Although DJ-1 directly bound the isolated microtubule-binding repeat region of tau protein, exposure of preformed tau seeds to DJ-1 did not diminish seeding activity in a biosensor cell model. These data reveal DJ-1 to be a holdase chaperone capable of engaging tau as a client in addition to α-synuclein. Our findings support a role for DJ-1 as part of an endogenous defense against the aggregation of these intrinsically disordered proteins.

Monomer-Promoting Asymmetric Kinetic Resolution-Alternating Copolymerization To Afford AAB-Type Copolyesters.

Living copolymerization of mixed monomers can enrich the diversity of copolymer materials with well-defined performance via controlling both monomers and stereosequences. However, periodic sequence-controlled living copolymerization of same-type monomers with more than two components in synthetic polymer science remains a challenge. In this work, a new method of monomer-promoting asymmetric kinetic resolution-alternating copolymerization can let a tricomponent mixture of l-lactide (S,S-LA or l-LA) and two enantiomeric isomers of racemic tropic acid cyclic esters (tropicolactone) be polymerized into sequence-controlled -(ASASBS)n- type biodegradable copolyesters (the subscript S presents the configuration and A and B present lactic acid units and tropic acid units, respectively), and diblock copolymers of -(ASASBS)n-b-(ARARBR)n- can further be obtained upon addition of R,R-LA (d-LA). Compared to previous asymmetric kinetic resolutions of racemic chemicals via polymerization or organic reactions, no enantiopure catalyst/initiator is required in this system. After the resolution and alternating copolymerization of S,S-LA and rac-tropicolactone, the ee value of unreacted tropicolactone can reach 99.4%. The alternating probability between tropicolactone and lactide monomers is more than 96% in periodic sequence polymers of -(ASASBS)n-. The tetracomponent mixture of rac-lactide and rac-tropicolactone can be copolymerized into an alternating copolymer with a -((ASASBS)x-ran-(ARARBR)y)n- structure, in which the stereoselective linkage probability of 95% after S,S-lactide (R,R-lactide) followed by S-tropicolactone (R-tropicolactone) keeps very high too.

Prevalence and Risk Factors of Pulmonary Embolism Combined with Tuberculosis and the Efficacy of Anticoagulation Combined with Anti-tuberculosis.

Objective: This retrospective study aimed to determine the prevalence and risk factors of combined pulmonary embolism (PE) among patients with pulmonary tuberculosis (TB), as well as evaluate the clinical efficacy of anticoagulation in combination with anti-tuberculosis therapy. Methods: A total of 96 TB patients were included in the study. Among them, 31 patients had combined PE (PE group) and 65 patients did not have PE (no-PE group). Various indicators including lung images, clinical symptoms, blood tests, coagulation function, and others were analyzed to identify risk factors for combined PE in TB patients. Within the PE group, patients were divided into a combined treatment group (received anticoagulation therapy alongside anti-tuberculosis treatment) and a control group (received only anti-tuberculosis treatment). The effectiveness of anticoagulation, serological indexes, and incidence of adverse reactions were compared between the two groups. Results: The prevalence of combined PE in TB patients was 32.29%. Encapsulated effusion or upper lobe predominance, dyspnea, and high creatinine levels were identified as risk factors for combined PE in TB patients. The combined treatment group showed a significantly higher anticoagulation efficiency rate (95.00%) compared to the control group (72.73%). After treatment, serum D-dimer levels were significantly lower in the rivaroxaban group compared to the warfarin group. The incidence of adverse reactions did not differ significantly between the two groups. Conclusion: Combined PE was found in 32.29% of TB patients. Encapsulated effusion or upper lobe predominance, dyspnea, and high creatinine levels were identified as risk factors for combined PE in TB patients. Anticoagulation combined with anti-tuberculosis therapy was effective and safe for managing TB patients with combined PE.

Tetrabutylammonium Halides as Selectively Bifunctional Catalysts Enabling the Syntheses of Recyclable High Molecular Weight Salicylic Acid-Based Copolyesters.

To synthesize high molecular weight poly(phenolic ester) via a living ring-opening polymerization (ROP) of cyclic phenolic ester monomers remains a critical challenge due to serious transesterification and back-biting reactions. Both phenolic ester bonds in monomer and polymer chains are highly active, and it is difficult so far to distinguish them. In this work, an unprecedented selectively bifunctional catalytic system of tetra-n-butylammonium chloride (TBACl) was discovered to mediate the syntheses of high molecular weight salicylic acid-based copolyesters via a living ROP of salicylate cyclic esters (for poly(salicylic methyl glycolide) (PSMG), Mn =361.8 kg/mol, Ð<1.30). Compared to previous catalysis systems, the side reactions were suppressed remarkably in this catalysis system because phenolic ester bond in monomer can be selectively cleaved over that in polymer chains during ROP progress. Mechanistic studies reveal that the halide anion and alkyl-quaternaryammonium cation work synergistically, where the alkyl-quaternaryammonium cation moiety interacts with the carbonyl group of substrates via non-classical hydrogen bonding. Moreover, these salicylic acid-based copolyesters can be recycled to dimeric monomer under solution condition, and can be recycled to original monomeric monomers without catalyst under sublimation condition.

Wolframin is a novel regulator of tau pathology and neurodegeneration.

Selective neuronal vulnerability to protein aggregation is found in many neurodegenerative diseases including Alzheimer's disease (AD). Understanding the molecular origins of this selective vulnerability is, therefore, of fundamental importance. Tau protein aggregates have been found in Wolframin (WFS1)-expressing excitatory neurons in the entorhinal cortex, one of the earliest affected regions in AD. The role of WFS1 in Tauopathies and its levels in tau pathology-associated neurodegeneration, however, is largely unknown. Here we report that WFS1 deficiency is associated with increased tau pathology and neurodegeneration, whereas overexpression of WFS1 reduces those changes. We also find that WFS1 interacts with tau protein and controls the susceptibility to tau pathology. Furthermore, chronic ER stress and autophagy-lysosome pathway (ALP)-associated genes are enriched in WFS1-high excitatory neurons in human AD at early Braak stages. The protein levels of ER stress and autophagy-lysosome pathway (ALP)-associated proteins are changed in tau transgenic mice with WFS1 deficiency, while overexpression of WFS1 reverses those changes. This work demonstrates a possible role for WFS1 in the regulation of tau pathology and neurodegeneration via chronic ER stress and the downstream ALP. Our findings provide insights into mechanisms that underpin selective neuronal vulnerability, and for developing new therapeutics to protect vulnerable neurons in AD.

Promising tacrine/huperzine A-based dimeric acetylcholinesterase inhibitors for neurodegenerative disorders: From relieving symptoms to modifying diseases through multitarget.

Neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, are devastating diseases in the elderly world, which are closely associated with progressive neuronal loss induced by a variety of genetic and/or environmental factors. Unfortunately, currently available treatments for neurodegenerative disorders can only relieve the symptoms but not modify the pathological processes. Over the past decades, our group by collaborating with Profs. Yuan-Ping Pang and Paul R. Carlier has developed three series of homo/hetero dimeric acetylcholinesterase inhibitors derived from tacrine and/or huperzine A. The representative dimers bis(3)-Cognitin (B3C), bis(12)-hupyridone, and tacrine(10)-hupyridone might possess disease-modifying effects through the modulation of N-methyl-d-aspartic acid receptors, the activation of myocyte enhancer factor 2D gene transcription, and the promotion of neurotrophic factor secretion. In this review, we summarize that the representative dimers, such as B3C, provide neuroprotection against a variety of neurotoxins via multiple targets, including the inhibitions of N-methyl-d-aspartic acid receptor with pathological-activated potential, neuronal nitric oxide synthase, and ß-amyloid cascades synergistically. More importantly, B3C might offer disease-modifying potentials by activating myocyte enhancer factor 2D transcription, inducing neuritogenesis, and promoting the expressions of neurotrophic factors in vitro and in vivo. Taken together, the novel dimers might offer synergistic disease-modifying effects, proving that dimerization might serve as one of the strategies to develop new generation of therapeutics for neurodegenerative disorders.

Improving Interlaminar Fracture Toughness and Impact Performance of Carbon Fiber/Epoxy Laminated Composite by Using Thermoplastic Fibers.

The effects of thermoplastic polyimide (PI) and polypropylene (PP) fibers and areal density of toughened layer on interlaminar fracture toughness and impact performance of carbon fiber/epoxy (CF/EP) laminated composites were studied. Mode I interlaminar fracture toughness (GIC) was analyzed via double cantilever beam (DCB) tests. When comparing for the toughener type, PI played a positive role in enhancing the mode-I fracture toughness, while PP was not effective due to the less fiber bridge formed during composite curing. The toughening effects of areal density of PI were further investigated by end notched flexure (ENF) testing and low velocity impact testing to better understand the toughening mechanisms. The results revealed that the toughening effect reached its best effectiveness when the areal density of toughened layer was 30 g/m2. Compared with the control group, GIC and GIIC of CF/EP laminated composite were increased by 98.49% and 84.07%, and Fmax and Ee were enhanced by 92.38% and 299.08% under low velocity impact. There is no obvious delamination phenomenon on the surface of laminates after low velocity impact, indicating the improved interlaminar and impact performance of laminated composite.

TiO2 seeded on nitrogen-doped porous carbon nanofibers for superior electrochemical performance as freestanding anodes of lithium-ion batteries.

Fibrous mats piled by nitrogen-doped porous carbon nanofibers with seeded TiO2 are fabricated and punched directly into circles as lithium-ion battery anodes. The seeding structure is composed of semi-wrapped TiO2 nanoparticles on carbon nanofibers (CNFs) coated with a thin layer of carbon. Synchronously, pores with various widths are formed on CNFs. As a freestanding anode, an initial discharge capacity of 615 mAh g-1 with a coulombic efficiency of 56% is reached, and 322 mAh g-1 is obtained after 100 cycles at a current density of 100 mA g-1. This is assigned to the increasing number of active sites for the lithium ion from pores with various widths and improved conductivity originating from nitrogen doping. Superior rate performance (179 mAh g-1 at the current density of 2000 mA g-1) under various current densities compared with that of other counterparts is attributed to the structural stability originating from the seeding structure with the help of the C-O-Ti bond. An additional 800 cycles are displayed at the current density of 2000 mA g-1, and superior stability is also exhibited.

Primary Tr1 cells from metastatic melanoma eliminate tumor-promoting macrophages through granzyme B- and perforin-dependent mechanisms.

In malignant melanoma, tumor-associated macrophages play multiple roles in promoting tumor growth, such as inducing the transformation of melanocytes under ultraviolet irradiation, increasing angiogenesis in melanomas, and suppressing antitumor immunity. Because granzyme B- and perforin-expressing Tr1 cells could specifically eliminate antigen-presenting cells of myeloid origin, we examined whether Tr1 cells in melanoma could eliminate tumor-promoting macrophages and how the interaction between Tr1 cells and macrophages could affect the growth of melanoma cells. Tr1 cells were characterized by high interleukin 10 secretion and low Foxp3 expression and were enriched in the CD4+CD49b+LAG-3+ T-cell fraction. Macrophages derived from peripheral blood monocytes in the presence of modified melanoma-conditioned media demonstrated tumor-promoting capacity, exemplified by improving the proliferation of cocultured A375 malignant melanoma cells. But when primary Tr1 cells were present in the macrophage-A375 coculture, the growth of A375 cells was abrogated. The conventional CD25+ Treg cells, however, were unable to inhibit macrophage-mediated increase in tumor cell growth. Further analyses showed that Tr1 cells did not directly eliminate A375 cells, but mediated the killing of tumor-promoting macrophages through the secretion of granzyme B and perforin. The tumor-infiltrating interleukin 10+Foxp3-CD4+ T cells expressed very low levels of granzyme B and perforin, possibly suggested the downregulation of Tr1 cytotoxic capacity in melanoma tumors. Together, these data demonstrated an antitumor function of Tr1 cells through the elimination of tumor-promoting macrophages, which was not shared by conventional Tregs.

CD4+ T cell-mediated cytotoxicity eliminates primary tumor cells in metastatic melanoma through high MHC class II expression and can be enhanced by inhibitory receptor blockade.

Metastatic melanoma is a rapidly progressing disease with high mortality rate and limited treatment options. Immunotherapy based on tumor-targeting cytotoxic T cell responses represents a promising strategy. To assist in its development, we examined the possibility and efficacy of using CD4+ cytotoxic T cells. The regulatory mechanisms controlling CD4+ T cell-mediated cytotoxicity were also investigated. We found that naturally occurring granzyme B and perforin-expressing CD4+ cytotoxic T cells can be recovered from metastatic melanoma patients at significantly elevated frequencies compared to those from healthy controls. These CD4+ cytotoxic T cells were also capable of killing autologous tumor cells harvested from metastatic melanoma, independent of CD8+ T cells or any other cell types. However, several restricting factors were observed. First, the cytolytic activity by CD4+ T cells required high MHC class II expression on melanoma cells, which was not satisfied in a subset of melanomas. Second, the granzyme B and perforin release by activated CD4+ cytotoxic T cells was reduced after coculturing with autologous melanoma cells, characterized by low LAMP-1 expression and low granzyme B and perforin secretion in the supernatant. This suggested that inhibitory mechanisms were present to suppress CD4+ cytotoxic T cells. Indeed, blockade of PD-1 and CTLA-4 had increased the cytolytic activity of CD4+ T cells but was only effective in MHC class II high but not MHC class II low melanomas. Together, our study showed that CD4+ T cell-mediated cytotoxicity could eliminate primary melanoma cells but the efficacy depended on MHC class II expression.

Antifungal effects of undecylenic acid on the biofilm formation of Candida albicans.

Undecylenic acid can effectively control skin fungal infection, but the mechanism of its fungal inhibition is unclear. Hyphal growth of Candida albicans (C. albicans) and biofilm formation have been well recognized as important virulence factors for the initiation of skin infection and late development of disseminated infection. In this study, we seek to investigate antifungal mechanisms of undecylenic acid by evaluating the virulence factors of C. albicans during biofilm formation. We found that undecylenic acid inhibits biofilm formation of C. albicans effectively with optimal concentration above 3 mM. In the presence of this compound, the morphological transition from yeast to filamentous phase is abolished ultimately when the concentration of undecylenic acid is above 4 mM. Meanwhile, the cell surface is crumpled, and cells display an atrophic appearance under scanning electron microscopy even with low concentration of drug treatment. On the other hand, the drug treatment decreases the transcriptions of hydrolytic enzymes such as secreted aspartic protease, lipase, and phospholipase. Hyphal formation related genes, like HWP1, are significantly reduced in transcriptional level in drug-treated biofilm condition as well. The down-regulated profile of these genes leads to a poorly organized biofilm in undecylenic acid treated environment.

MER5101, a novel Aß1-15:DT conjugate vaccine, generates a robust anti-Aß antibody response and attenuates Aß pathology and cognitive deficits in APPswe/PS1ΔE9 transgenic mice.

Active amyloid-ß (Aß) immunotherapy is under investigation to prevent or treat early Alzheimer's disease (AD). In 2002, a Phase II clinical trial (AN1792) was halted due to meningoencephalitis in ∼6% of the AD patients, possibly caused by a T-cell-mediated immunological response. Thus, generating a vaccine that safely generates high anti-Aß antibody levels in the elderly is required. In this study, MER5101, a novel conjugate of Aß1-15 peptide (a B-cell epitope fragment) conjugated to an immunogenic carrier protein, diphtheria toxoid (DT), and formulated in a nanoparticular emulsion-based adjuvant, was administered to 10-month-old APPswe/PS1ΔE9 transgenic (Tg) and wild-type (Wt) mice. High anti-Aß antibody levels were observed in both vaccinated APPswe/PS1ΔE9 Tg and Wt mice. Antibody isotypes were mainly IgG1 and IgG2b, suggesting a Th2-biased response. Restimulation of splenocytes with the Aß1-15:DT conjugate resulted in a strong proliferative response, whereas proliferation was absent after restimulation with Aß1-15 or Aß1-40/42 peptides, indicating a cellular immune response against DT while avoiding an Aß-specific T-cell response. Moreover, significant reductions in cerebral Aß plaque burden, accompanied by attenuated microglial activation and increased synaptic density, were observed in MER5101-vaccinated APPswe/PS1ΔE9 Tg mice compared with Tg adjuvant controls. Last, MER5101-immunized APPswe/PS1ΔE9 Tg mice showed improvement of cognitive deficits in both contextual fear conditioning and the Morris water maze. Our novel, highly immunogenic Aß conjugate vaccine, MER5101, shows promise for improving Aß vaccine safety and efficacy and therefore, may be useful for preventing and/or treating early AD.

Effects of Litsea cubeba Essential Oil-Chitosan/Corn Starch Composite Films on the Quality and Shelf-Life of Strawberry (Fragaria × ananassa).

In this work, we have developed a composite chitosan film incorporating the Litsea cubeba essential oil (LCEO) and starch with good physical properties, and investigated the effect of coating strawberries with this composite film. The best formula of the LCEO/chitosan/corn starch/glycerol (LCEO/CH/CS/gly) composite films is 0.25% LCEO, 2.75% CH, 0.40% corn starch, and 0.75% glycerol. Coating strawberries with CH/CS/gly film or LCEO/CH/CS/gly films resulted in significantly lower respiration intensity and a slower decay rate, much slower decreases in the firmness, and reductions in the sugar and ascorbic acid content of the fruit during storage (p < 0.05). The coatings also led to a much slower accumulation of malondialdehyde and anthocyanins (p < 0.05). The LCEO/CH/CS/gly film was generally more effective than the CH/CS/gly film; however, the effect was more obvious in the later stages of storage. Thus, coating strawberries with CH/CS/gly film or LCEO/CH/CS/gly film can be a viable method for extending the shelf-life of the fruit.

Global disease burden linked to diet high in red meat and colorectal cancer from 1990 to 2019 and its prediction up to 2030.

Background: Numerous studies have already identified an association between excessive consumption of red meat and colorectal cancer (CRC). However, there has been a lack of detailed understanding regarding the disease burden linked to diet high in red meat and CRC. Objective: We aim to offer evidence-based guidance for developing effective strategies that can mitigate the elevated CRC burden in certain countries. Methods: We used the data from the Global Burden of Disease (GBD) Study 2019 to evaluate global, regional, and national mortality rates and disability-adjusted Life years (DALYs) related to diet high in red meat. We also considered factors such as sex, age, the socio-demographic index (SDI), and evaluated the cross-national inequalities. Furthermore, we utilized DALYs data from 204 countries and regions to measure cross-country inequalities of CRC by calculating the slope index of inequality and concentration index as standard indicators of absolute and relative inequalities. Discussion: The results show that globally, the age-standardized mortality rate (ASMR) and age-standardized disability adjusted life year rate (ASDR) related to CRC due to diet high in red meat have decreased, with estimated annual percent change (EAPCs) of -0.32% (95% CI -0.37 to -0.28) and-0.18% (95% CI -0.25 to -0.11). Notably, the burden was higher among males and the elderly. The slope index of inequality rose from 22.0 (95% CI 18.1 to 25.9) in 1990 to 32.9 (95% CI 28.3 to 37.5) in 2019 and the concentration index fell from 59.5 (95% CI 46.4 to 72.6) in 1990 to 48.9 (95% CI 34.6 to 63.1) in 2019. Also, according to our projections, global ASDR and ASMR might tend to increase up to 2030. Conclusion: ASMR and ASDR for CRC associated with high red meat diets declined globally from 1990 to 2019, but the absolute number of cases is still rising, with men and the elderly being more affected. CRC associated with diets high in red meat exhibits significant income inequality, placing a disproportionate burden on wealthier countries. Moreover, according to our projections, ASMR and ASDR are likely to increase globally by 2030. In order to address this intractable disease problem, understanding changes in global and regional epidemiologic trends is critical for policy makers and others.

A single-cell and spatial RNA-seq database for Alzheimer's disease (ssREAD).

Alzheimer's Disease (AD) pathology has been increasingly explored through single-cell and single-nucleus RNA-sequencing (scRNA-seq & snRNA-seq) and spatial transcriptomics (ST). However, the surge in data demands a comprehensive, user-friendly repository. Addressing this, we introduce a single-cell and spatial RNA-seq database for Alzheimer's disease (ssREAD). It offers a broader spectrum of AD-related datasets, an optimized analytical pipeline, and improved usability. The database encompasses 1,053 samples (277 integrated datasets) from 67 AD-related scRNA-seq & snRNA-seq studies, totaling 7,332,202 cells. Additionally, it archives 381 ST datasets from 18 human and mouse brain studies. Each dataset is annotated with details such as species, gender, brain region, disease/control status, age, and AD Braak stages. ssREAD also provides an analysis suite for cell clustering, identification of differentially expressed and spatially variable genes, cell-type-specific marker genes and regulons, and spot deconvolution for integrative analysis. ssREAD is freely available at https://bmblx.bmi.osumc.edu/ssread/ .

Bidentate selenium-based chalcogen bond catalyzed cationic polymerization of p-methoxystyrene.

The application of selenium-based non-covalent bond catalysis in living cationic polymerization has rarely been reported. In this work, the cationic polymerization of p-methoxystyrene (pMOS) was performed using a bidentate selenium bond catalyst - a new water-tolerant Lewis acid catalyst. A polymer with controllable molecular weight and narrow molecular weight distribution can be obtained at room temperature, with a maximum molecular weight of 23.3 kDa. This selenium bond compound can also catalyze the controllable cationic polymerization of p-methoxy styrene under environmental conditions. By changing the monomer feeding ratio, a secondary feeding experiment and DFT analysis, it is shown that the selenium bond catalyst can induce polymer chain growth by reversibly activating dormant covalent bonds (C-OH).

ssREAD: A Single-cell and Spatial RNA-seq Database for Alzheimer's Disease.

Alzheimer's Disease (AD) is a neurodegenerative malady predominantly affecting the elderly and exhibits its debilitating effects on a dementia-prone population. Recently, the advent of innovative technologies, such as single-cell and single-nucleus RNA-sequencing (scRNA-seq & snRNA-seq) and spatial transcriptomics (ST), has reformed our investigative approaches toward comprehending AD's neuropathological intricacies and underpinning regulatory mechanisms, encompassing sub-cellular, cellular, and spatial dimensions. In light of the overwhelming proliferation of single-cell and ST data associated with AD, the imperative for a comprehensive, user-friendly database that addresses the scientific community's analytical demands has never been more paramount. Introduced initially in 2020, scREAD presented itself as a pioneering repository that systematized publicly available scRNA-seq and snRNA-seq datasets derived from post-mortem human brain tissues and mouse models mirroring AD pathology. Here, we introduce ssREAD, a substantial upgrade over scREAD, enriching the platform with a broader spectrum of datasets, an optimized analytical pipeline, and enhanced usability and visibility. Specifically, ssREAD amalgamates an impressive portfolio of over 189 datasets extracted from 35 distinct AD-related scRNA-seq and snRNA-seq studies, encompassing a staggering 2,572,355 cells. In addition, we have diligently curated and archived 300 ST datasets, originating from 12 human and mouse brain studies, which include two focused on AD and ten control studies. Every dataset within our repository is meticulously annotated, bearing critical identifiers including species, gender, brain region, disease/control status, age, and AD stages. Besides the collection of above datasets in ssREAD, it delivers an exhaustive analysis suite offering cell clustering and annotation, inference of differentially expressed and spatially variable genes, identification of cell-type-specific marker genes and regulons, and spot deconvolution for integrative analysis of ST and scRNA-seq & snRNA-seq data from public domains. All these resources are freely accessible through a user-friendly, consolidated web portal available at https://bmblx.bmi.osumc.edu/ssread/.

Original surgical technique for the treatment of patellofemoral instability after failure of conservative treatment.

INTRODUCTION: Acute patellar dislocation is a common but serious injury that can significantly impact a patient's functional prognosis. The objective of this retrospective study is to evaluate the clinical outcomes of arthroscopic medial patellofemoral ligament (MPFL) reconstruction and plication of the medial patellar retinaculum using suture anchors in adolescent patients with first-time acute patellar dislocation (APD) and MPFL insertion injury. HYPOTHESIS: Tightening repair of the medial retinaculum complex can result in favorable clinical and functional outcomes in this patient population. MATERIALS AND METHODS: A total of 84 adolescent patients with first-time APD and with an average age of 15.5 years (10-22) were included in the study. Of these patients, 61 (7 male and 54 female) underwent arthroscopic suture anchor plication for medial patellar retinaculum, while the other 23 were successfully treated non-operatively. Radiographic outcomes, including the congruence angle (CA), lateral patellofemoral angle (LPA), and patellar tilt angle (PTA), were evaluated preoperatively and at the last follow-up visit in the surgical group. Functional outcomes were assessed using the Lille Patello-Femoral Score, Lysholm Score, and Kujala Score at the same time points. In addition, the surgical and non-operative treatment success groups were compared in terms of both radiographic and functional outcomes. RESULTS: Mean follow-up was 40.9 months (24-60). Fifty-nine knees showed excellent or good results postoperatively, 2 patients had a recurrent patellar subluxation. The Lille Patello-Femoral Score was 96.9±4.7 at the last follow-up. The subjective Lysholm Score and Kujala Score improved significantly, from 58.6 to 91.9 and from 60.4 to 88.9, respectively. The radiographic CA, LPA and PTA improved significantly, from 19.8±2.1° to -6.7±1.7°, from -7.4±2.2° to 5.7±1.8° and from 23.8±2.9° to 12.3±2.3°, respectively. There was no statistically significant difference in functional and radiographic assessments between the success with non-operative treatment group and the surgery group. CONCLUSION: The results of this study suggest that arthroscopic MPFL insertion reconstruction and plication using suture anchors, which is less invasive and improves patella stability, can lead to favorable clinical and functional outcomes in adolescent patients with first-time acute patellar dislocation and insertion injury. This treatment approach should be considered as a viable option for this patient population. LEVEL OF EVIDENCE: IV; monocentric retrospective descriptive study.