Tailor-Made α-Glucans by Engineering the Processivity of α-Glucanotransferases via Tunnel-Cleft Active Center Interconversions.

The function of polysaccharides is intimately associated with their size, which is largely determined by the processivity of transferases responsible for their synthesis. A tunnel active center architecture has been recognized as a key factor that governs processivity of several glycoside hydrolases (GHs), e.g., cellulases and chitinases. Similar tunnel architecture is also observed in the Limosilactobacillus reuteri 121 GtfB (Lr121 GtfB) α-glucanotransferase from the GH70 family. The molecular element underpinning processivity of these transglucosylases remains underexplored. Here, we report the synthesis of the smallest (α1 → 4)-α-glucan interspersed with linear and branched (α1 → 6) linkages by a novel 4,6-α-glucanotransferase from L. reuteri N1 (LrN1 GtfB) with an open-clefted active center instead of the tunnel structure. Notably, the loop swapping engineering of LrN1 GtfB and Lr121 GtfB based on their crystal structures clarified the impact of the loop-mediated tunnel/cleft structure at the donor subsites -2 to -3 on processivity of these α-glucanotransferases, enabling the tailoring of both product sizes and substrate preferences. This study provides unprecedented insights into the processivity determinants and evolutionary diversification of GH70 α-glucanotransferases and offers a simple route for engineering starch-converting α-glucanotransferases to generate diverse α-glucans for different biotechnological applications.

Intelligent Fusion of Multi-Source Senses Information for Identifying the Nature of Five Flavors in Chinese Medicine: A Comprehensive Study of Five Classifications.

Objective: To develop a classification model for the five flavors of Chinese medicine using advanced multi-source intelligent sensory information fusion technology. The primary aim is to investigate the feasibility of applying this model to classify and identify the flavors of various Chinese medicines effectively. Methods: We selected 122 representative Chinese medicines, each exhibiting a single distinct flavor (sour, pungent, salty, sweet, bitter), along with 14 common foods. Utilizing the nature and flavors of these decoction pieces specified in Chinese Pharmacopeia (ChP)2020 and the inherent attributes of food components, we obtained valuable data from various sensors, including the PEN3 electronic nose, ASTREE electronic tongue, and SA402B electronic tongue. We then collected single-source data matrices from these sample sensors and a multi-source data matrix that combined the data from all sensors. Using discriminant analysis (DA), principal component analysis-discriminant analysis (PCA-DA), and K-nearest neighbor algorithm (KNN) three kinds of chemometric methods were used to establish five flavors and five-category discrimination models. The results were comprehensively evaluated with the highest correct rate of the model of leave-one-out cross-validation as the index. Results: Upon leave-one-out cross-validation, the correct judgment rate of the five flavors, five-category two-source fusion DA discrimination model (83.8%; ASTREE + SA402B) was significantly higher than the correct judgment rate of the single-source optimal DA and KNN model (73.5%; ASTREE). Following full-sample modeling, the correct judgment rate of the five flavors, five-category three-source fusion DA discrimination model (94.9%; PEN3+ASTREE+SA402B) rose substantially. This was higher than the correct judgment rate of the single-source optimal DA model (77.9%; ASTREE) and slightly higher than the two-source optimal correct judgment rate (89.7%; PEN3 + ASTREE). Conclusions: Compared to single-source identification, multi-source intelligent senses information fusion (MISIF) significantly improved accuracy, providing a new outlook for identifying flavor in Chinese medicine.

Self-healing and corrosion-sensing multifunctional coatings containing pH-sensitive TiO2-based composites.

Polyelectrolyte-encapsulated nanocontainers can effectively respond to changes of pH and thus control the on-demand release of corrosion inhibitors. A pH-responsive release system (Phen-Tpp@MTNs-PDDA) was developed based on the cationic polyelectrolyte poly dimethyl diallyl ammonium chloride (PDDA) encapsulated mesoporous TiO2 nanocontainers (MTNs) loaded with 1,10-phenanthroline (Phen) and tripolyphosphate ions (Tpp) corrosion inhibitors. The epoxy coating (EP) embedded with Phen-Tpp@MTNs-PDDA (Phen-Tpp@MTNs-PDDA/EP) demonstrates superior self-healing properties and confers long-term protection on the metal substrate through the cooperative effect of Phen and Tpp. Simultaneously, this hybrid coating is endowed with corrosion sensing capability based on the color development originating from the interaction of Phen and carbon steel. This self-healing and corrosion-sensing multifunctional coating provides an effective strategy for the corrosion protection of metals.

Mechanisms involved in the regulation of mitochondrial quality control by PGAM5 in heart failure.

Heart failure refers to a group of clinical syndromes in which various heart diseases lead to the inability of cardiac output to meet the metabolic needs of the body's tissues. Cardiac metabolism requires enormous amounts of energy; thus, impaired myocardial energy metabolism is considered a key factor in the occurrence and development of heart failure. Mitochondria serve as the primary energy source for cardiomyocytes, and their regular functionality underpins healthy cardiac function. The mitochondrial quality control system is a crucial mechanism for regulating the functionality of cardiomyocytes, and any abnormality in this system can potentially impact the morphology and structure of mitochondria, as well as the energy metabolism of cardiomyocytes. PGAM5, a multifunctional protein, plays a key role in the regulation of mitochondrial quality control through multiple pathways. Therefore, abnormal PGAM5 function is closely related to mitochondrial damage. This article reviews the mechanism of PGAM5's involvement in the regulation of the mitochondrial quality control system in the occurrence and development of heart failure, thereby providing a theoretical basis for future in-depth research.

Towards low-temperature dendrite-free zinc anode by constructing functional MXene buffer layer with duplex zincophilic sites.

Dendrite growth and side reactions of zinc metal anode have severely limited the practical application of aqueous zinc ion batteries (AZIBs). Herein, we introduce an artificial buffer layer composed of functional MXene (Ti3CN) for zinc anodes. The synthesized Ti3CN exhibits superior conductivity and features duplex zincophilic sites (N and F). These characteristics facilitate the homogeneous deposition of Zn2+, accelerate the desolvation process of hydrated Zn2+, and reduce the nucleation overpotential. The Ti3CN-protected Zn anode demonstrates significantly enhanced reversibility compared to bare Zn anode during long-term cycling, achieving a cumulative plating capacity of 10,000 mAh cm-2 at 10 mA cm-2. In Ti3CN-Zn||Cu asymmetric cell, it maintains nearly 100 % Coulombic efficiency over 2500 cycles at 2 mA cm-2. Furthermore, the assembled Ti3CN-Zn//δ-K0.51V2O5 (KVO) full cell exhibit a low capacity decay rate of 0.002 % per cycle at 5 A/g. Even at 0 °C, the Ti3CN-Zn symmetric cell maintains steady cycling for 2000 h. This study introduces a novel approach for designing artificial solid electrolyte interlayers for commercial AZIBs.

Efficacy and safety of guselkumab in patients with active psoriatic arthritis who had inadequate efficacy and/or intolerance to one prior tumor necrosis factor inhibitor: study protocol for SOLSTICE, a phase 3B, multicenter, randomized, double-blind, placebo-controlled study.

BACKGROUND: Tumor necrosis factor inhibitors (TNFi) are frequently chosen as the first biologic for patients with psoriatic arthritis (PsA). Given that many patients with PsA are TNFi inadequate responders (TNF-IR; either inadequate efficacy or intolerance), treatments utilizing alternative mechanisms of action are needed. In phase 3 studies, the fully human interleukin (IL)-23p19 subunit-inhibitor, guselkumab, was efficacious in patients with active PsA, including TNFi-IR. Efficacy was generally consistent between TNFi-naïve and TNFi-experienced cohorts; however, in the latter, higher response rates have been observed with the Q4W dosing regimen relative to the Q8W dosing regimen for some endpoints, suggesting the need to evaluate whether more frequent dosing may provide an incremental clinical benefit for TNFi-IR patients. METHODS: The phase 3b SOLSTICE study will assess guselkumab efficacy and safety in TNFi-IR PsA patients. Eligibility criteria include a PsA diagnosis for ≥ 6 months; active disease (≥ 3 swollen, ≥ 3 tender joints, C-reactive protein ≥ 0.3 mg/dL); and inadequate efficacy with, and/or intolerance to, one prior TNFi. Participants will be randomized 1:1:1 to guselkumab Q4W or Q8W or placebo→guselkumab Q4W (at Week 24). The primary endpoint is the proportion of patients achieving ≥ 20% improvement in the American College of Rheumatology criteria (ACR20) at Week 24. Major secondary endpoints include ACR50, ACR70; an Investigator's Global Assessment (IGA) of psoriasis score of 0/1 plus ≥ 2-grade reduction and ≥ 90% improvement in Psoriasis Area and Severity Index (both among patients with ≥ 3% body surface area affected by psoriasis and baseline IGA ≥ 2); minimal/very low disease activity; and changes from baseline in Health Assessment Questionnaire-Disability Index, the 36-item Short-Form Health Survey Physical Component Summary, and Functional Assessment of Chronic Illness Therapy-Fatigue scores. The target sample size (N = 450) is estimated to provide > 90% power in detecting differences between each guselkumab group and the placebo group for the primary endpoint assuming a 2-sided α = 0.05. Cochran-Mantel-Haenszel testing and analyses of covariance will be used to compare efficacy for binary and continuous endpoints, respectively. DISCUSSION: Findings from the phase 3b SOLSTICE study, the design of which was informed by results from previously conducted phase 3 studies, is expected to provide important efficacy and safety information on guselkumab therapy in TNFi-IR patients with PsA. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov, NCT04936308, on 23 June 2021.

Successful management of postpartum venous thrombosis following splenectomy for traumatic splenic rupture: a case report.

Traumatic splenic rupture is rare in pregnant women; and multiple venous thromboses of the portal vein system, inferior vena cava and ovarian vein after caesarean section and splenectomy for splenic rupture has not been previously reported. This case report describes a case of multiple venous thromboses after caesarean section and splenectomy for traumatic splenic rupture in late pregnancy. A 34-year-old G3P1 female presented with abdominal trauma at 33+1 weeks of gestation. After diagnosis of splenic rupture, she underwent an emergency caesarean section and splenectomy. Multiple venous thromboses developed during the recovery period. The patient eventually recovered after anticoagulation therapy with low-molecular-weight heparin and warfarin. These findings suggest that in patients that have had a caesarean section and a splenectomy, which together might further increase the risk of venous thrombosis, any abdominal pain should be thoroughly investigated and thrombosis should be ruled out, including the possibility of multiple venous thromboses. Anticoagulant therapy could be extended after the surgery.

The diagnostic value of metagenomics next-generation sequencing in HIV-infected patients with suspected pulmonary infections.

Background: Traditional microbiological detection methods used to detect pulmonary infections in people living with HIV (PLHIV) are usually time-consuming and have low sensitivity, leading to delayed treatment. We aimed to evaluate the diagnostic value of metagenomics next-generation sequencing (mNGS) for microbial diagnosis of suspected pulmonary infections in PLHIV. Methods: We retrospectively analyzed PLHIV who were hospitalized due to suspected pulmonary infections at the sixth people hospital of Zhengzhou from November 1, 2021 to June 30, 2022. Bronchoalveolar lavage fluid (BALF) samples of PLHIV were collected and subjected to routine microbiological examination and mNGS detection. The diagnostic performance of the two methods was compared to evaluate the diagnostic value of mNGS for unknown pathogens. Results: This study included a total of 36 PLHIV with suspected pulmonary infections, of which 31 were male. The reporting period of mNGS is significantly shorter than that of CMTs. The mNGS positive rate of BALF samples in PLHIV was 83.33%, which was significantly higher than that of smear and culture (44.4%, P<0.001). In addition, 11 patients showed consistent results between the two methods. Futhermore, mNGS showed excellent performance in identifying multi-infections in PLHIV, and 27 pathogens were detected in the BALF of 30 PLHIV by mNGS, among which 15 PLHIV were found to have multiple microbial infections (at least 3 pathogens). Pneumocystis jirovecii, human herpesvirus type 5, and human herpesvirus type 4 were the most common pathogen types. Conclusions: For PLHIV with suspected pulmonary infections, mNGS is capable of rapidly and accurately identifying the pathogen causing the pulmonary infection, which contributes to implement timely and accurate anti-infective treatment.

Fatty Acid Binding Protein-4 Silencing Inhibits Ferroptosis to Alleviate Lipopolysaccharide-induced Injury of Renal Tubular Epithelial Cells by Blocking Janus Kinase 2/Signal Transducer and Activator of Transcription 3 Signaling.

Sepsis-induced kidney injury (SAKI) has been frequently established as a prevailing complication of sepsis which is linked to unfavorable outcomes. Fatty acid-binding protein-4 (FABP4) has been proposed as a possible target for the treatment of SAKI. In the current work, we aimed to explore the role and underlying mechanism of FABP4 in lipopolysaccharide (LPS)-induced human renal tubular epithelial cell damage. In LPS-induced human kidney 2 (HK2) cells, FABP4 expression was tested by the reverse transcription-quantitative polymerase chain reaction and Western blot. Cell counting kit-8 method assayed cell viability. Inflammatory levels were detected using the enzyme-linked immunosorbent assay. Immunofluorescence staining measured the nuclear translocation of nuclear factor kappa B p65. Thiobarbituric acid-reactive substances assay and C11 BODIPY 581/591 probe were used to estimate the level of cellular lipid peroxidation. Fe2+ content was examined by the kit. In addition, the expression of proteins related to inflammation-, ferroptosis- and Janus kinase 2 (JAK2)/signal transducer, and activator of transcription 3 (STAT3) signaling was detected by the Western blot analysis. The results revealed that FABP4 was significantly upregulated in LPS-treated HK2 cells, the knockdown of which elevated the viability, whereas alleviated the inflammation and ferroptosis in HK2 cells challenged with LPS. In addition, down-regulation of FABP4 inactivated JAK2/STAT3 signaling. JAK2/STAT3 stimulator (colivelin) and ferroptosis activator (Erastin) partially restored the effects of FABP4 interference on LPS-triggered inflammation and ferroptosis in HK2 cells. Together, FABP4 knockdown inhibited ferroptosis to alleviate LPS-induced injury of renal tubular epithelial cells through suppressing JAK2/STAT3 signaling.

18F-FDG PET/CT findings in nevoid basal cell carcinoma syndrome: a systematic review and a new case report.

BACKGROUND: To demonstrate and analyze the 18F-FDG positron emission tomography/computed tomography (PET/CT) findings in this rare nevoid basal cell carcinoma syndrome (NBCCS). CASE PRESENTATION: A 71-year-old woman with the left invasive breast cancer was treated with hormone therapy for six months and underwent the 18F-FDG PET/CT examination for efficacy evaluation. 18F-FDG PET/CT revealed the improvement after treatment and other unexpected findings, including multiple nodules on the skin with 18F-FDG uptake, bone expansion of cystic lesions in the bilateral ribs, ectopic calcifications and dilated right ureter. She had no known family history. Then, the patient underwent surgical excision of the all skin nodules and the postoperative pathology were multiple basal cell carcinomas. Finally, the comprehensive diagnosis of NBCCS was made. The patient was still in follow-up. Additionally, we have summarized the reported cases (n = 3) with 18F-FDG PET/CT from the literature. CONCLUSIONS: It is important to recognize this syndrome on 18F-FDG PET/CT because of different diagnoses and therapeutic consequences.

[Clinical phenotype and genetic characteristics of a Chinese pedigree affected with Spastic paraplegia type 5A].

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a Chinese pedigree affected with Spastic paraplegia type 5A (SPG5A). METHODS: A pedigree suspected for Hereditary spastic paraplegia (HSP) at Henan Children's Hospital on August 15 2022 was selected as the study subject. Clinical data of the pedigree was collected. Peripheral blood samples were collected from members of the pedigree. Following extraction of genomic DNA, trio-WGS was carried out, and candidate variant was verified by Sanger sequencing. RESULTS: The child, a 1-year-old boy, had presented with microcephaly, hairy face and dorsal side of distal extremities and trunk, intellectual and motor development delay, increased muscle tone of lower limbs, hyperreflexes of bilateral knee tendons, and positive pathological signs. His parents and sister both had normal phenotypes. Trio-WGS revealed that the child has harbored a homozygous c.1250G>A (p.Arg417His) variant of the CYP7B1 gene, for which his mother was heterozygous, the father and sister were of the wild type. The variant was determined to have originated from maternal uniparental disomy (UPD). The result of Sanger sequencing was in keeping with the that of trio-WGS. SPG5A due to maternal UPD of chromosome 8 was unreported previously. CONCLUSION: The child was diagnosed with SPG5A, a complex type of HSP, for which the homozygous c.1250G>A variant of the CYP7B1 gene derived from maternal UPD may be accountable.

HD-Zip proteins modify floral structures for self-pollination in tomato.

Cleistogamy is a type of self-pollination that relies on the formation of a stigma-enclosing floral structure. We identify three homeodomain-leucine zipper IV (HD-Zip IV) genes that coordinately promote the formation of interlocking trichomes at the anther margin to unite neighboring anthers, generating a closed anther cone and cleistogamy (flower morphology necessitating strict self-pollination). These HD-Zip IV genes also control style length by regulating the transition from cell division to endoreduplication. The expression of these HD-Zip IV genes and their downstream gene, Style 2.1, was sequentially modified to shape the cleistogamy morphology during tomato evolution and domestication. Our results provide insights into the molecular basis of cleistogamy in modern tomato and suggest targets for improving fruit set and preventing pollen contamination in genetically modified crops.

Milk: A Natural Guardian for the Gut Barrier.

The gut barrier plays an important role in health maintenance by preventing the invasion of dietary pathogens and toxins. Disruption of the gut barrier can cause severe intestinal inflammation. As a natural source, milk is enriched with many active constituents that contribute to numerous beneficial functions, including immune regulation. These components collectively serve as a shield for the gut barrier, protecting against various threats such as biological, chemical, mechanical, and immunological threats. This comprehensive review delves into the active ingredients in milk, encompassing casein, α-lactalbumin, ß-lactoglobulin, lactoferrin, the milk fat globular membrane, lactose, transforming growth factor, and glycopeptides. The primary focus is to elucidate their impact on the integrity and function of the gut barrier. Furthermore, the implications of different processing methods of dairy products on the gut barrier protection are discussed. In conclusion, this study aimed to underscore the vital role of milk and dairy products in sustaining gut barrier health, potentially contributing to broader perspectives in nutritional sciences and public health.

Application of dual chemotherapeutic drug delivery system based on metal-organic framework platform in enhancing tumor regression for breast cancer research.

The nanomedicine system based on dual drug delivery systems (DDDs) can significantly enhance the efficacy of tumor treatment. Herein, a metal-organic framework, Zeolite imidazole salt frames 8 (ZIF-8), was successfully utilized as a carrier to load the dual chemotherapeutic drugs doxorubicin (DOX) and camptothecin (CPT), named DOX/CPT@ZIF-8 (denoted as DCZ), and their inhibitory effects on 4T1 breast cancer cells were evaluated. The study experimentally demonstrated the synergistic effects of the dual chemotherapeutic drugs within the ZIF-8 carrier and showed that the ZIF-8 nano-carrier loaded with the dual drugs exhibited stronger cytotoxicity and inhibitory effects on 4T1 breast cancer cells compared to single-drug treatment. The use of a ZIF-8-based dual chemotherapeutic drug carrier system highlighted its potential advantages in suppressing 4T1 breast cancer cells.

Molecular Imaging of Alzheimer's Disease-Related Sigma-1 Receptor in the Brain via a Novel Ru-Mediated Aromatic 18F-deoxyfluorination Probe.

Sigma-1 receptor (σ1R) is an intracellular protein implicated in a spectrum of neurodegenerative conditions, notably Alzheimer's disease (AD). Positron emission tomography (PET) imaging of brain σ1R could provide a powerful tool for better understanding the underlying pathomechanism of σ1R in AD. In this study, we successfully developed a 18F-labeled σ1R radiotracer [18F]CNY-05 via an innovative ruthenium (Ru)-mediated 18F-deoxyfluorination method. [18F]CNY-05 exhibited preferable brain uptake, high specific binding, and slightly reversible pharmacokinetics within the PET scanning time window. PET imaging of [18F]CNY-05 in nonhuman primates (NHP) indicated brain permeability, metabolic stability, and safety. Moreover, autoradiography and PET studies of [18F]CNY-05 in the AD mouse model found a significantly decreased brain uptake compared to that in wild-type mice. Collectively, we have provided a novel 18F-radiolabeled σ1R PET probe, which enables visualizing brain σ1R in health and neurological diseases.

Characterization of the complete chloroplast genome sequence of Camellia tetracocca (Theaceae).

Camellia tetracocca H.T. Chang 1981 is an important wild relative of cultivated tea plants. Its leaves are widely used by local people to make tea, showing great economic and breeding values. We here report the complete chloroplast genome of C. tetracocca using Illumina sequencing technology. The complete chloroplast genome of C. tetracocca is 157,026 bp in length, and structurally contains a pair of inverted repeat regions (IRa and IRb, 26,052 bp) separated by a large single-copy region (LSC, 86,669 bp) and a small single-copy region (SSC, 18,253 bp). It is composed of 131 predicted genes, including 86 protein-coding genes, 37 transfer RNA genes, and eight ribosomal RNA genes. The overall GC content is 37.31%. Phylogenetic analysis among four Camellia species and 11 other close species reveals a close relationship between C. tetracocca and C. gymnogyna.

Reduced contrast sensitivity function is correlated with changes to cone photoreceptors in simple high myopia.

Purpose: To investigate the contrast sensitivity function (CSF) changes in simple high myopia (SHM) and evaluate the correlations between these changes with the early changes in the retinal microstructure. Methods: This prospective study comprised 81 subjects, 20 with emmetropia (EM), 26 with low myopia and moderate myopia (LM/MM), and 35 with SHM. The area under the log CSF curve (AULCSF) and the cut-off spatial frequency (Cut-off SF) were employed as measures of CSF. Adaptive optics (AO) was employed to quantify the cone density, spacing, and regularity. The thickness and blood flow of the retinal sublayers were determined from vertical and horizontal optical coherence tomography angiography (OCTA) A-scans. Swept-source optical coherence tomography (SS-OCT) was employed to analyze the choroidal thickness (CT) and choroidal vascularity using a custom algorithm. Differences in the retinal and choroidal parameters, cone distribution, AULCSF, and Cut-off SF were compared among the three groups. Multivariate linear mixed models were used to elucidate the associations between photoreceptor morphological alterations, retinal and choroidal parameters, and AULCSF. Results: The AULCSF and Cut-off SF were significantly lower in the SHM group compared to the EM and LM groups (p < 0.05). The SHM group had less cone density, larger cone spacing, and lower cone regularity than the EM and LM/MM groups (p < 0.05). Moreover, the thickness of the inner segment of photoreceptors (IS), retinal pigment epithelium (RPE) layer and choroid were reduced, and the outer segment of photoreceptors (OS) was thicker in the SHM group compared to the EM and LM/MM groups (all p < 0.05). A longer axial length (AL) was correlated with decreased AULCSF, cone density, and cone spacing (r = -0.800 to 0.752, all p < 0.050). Additionally, decreased CSF was correlated with lower cone density (r = 0.338, p = 0.035). Conclusion: Decreased contrast sensitivity was observed in patients with SHM and cone density was significantly correlated with reduced AUCSF.

Diffusion models in bioinformatics and computational biology.

Denoising diffusion models embody a type of generative artificial intelligence that can be applied in computer vision, natural language processing and bioinformatics. In this Review, we introduce the key concepts and theoretical foundations of three diffusion modelling frameworks (denoising diffusion probabilistic models, noise-conditioned scoring networks and score stochastic differential equations). We then explore their applications in bioinformatics and computational biology, including protein design and generation, drug and small-molecule design, protein-ligand interaction modelling, cryo-electron microscopy image data analysis and single-cell data analysis. Finally, we highlight open-source diffusion model tools and consider the future applications of diffusion models in bioinformatics.

Deep Self-Reconstruction Fusion Similarity Hashing for the Diagnosis of Alzheimer's Disease on Multi-Modal Data.

The pathogenesis of Alzheimer's disease (AD) is extremely intricate, which makes AD patients almost incurable. Recent studies have demonstrated that analyzing multi-modal data can offer a comprehensive perspective on the different stages of AD progression, which is beneficial for early diagnosis of AD. In this paper, we propose a deep self-reconstruction fusion similarity hashing (DS-FSH) method to effectively capture the AD-related biomarkers from the multi-modal data and leverage them to diagnose AD. Given that most existing methods ignore the topological structure of the data, a deep self-reconstruction model based on random walk graph regularization is designed to reconstruct the multi-modal data, thereby learning the nonlinear relationship between samples. Additionally, a fused similarity hash based on anchor graph is proposed to generate discriminative binary hash codes for multi-modal reconstructed data. This allows sample fused similarity to be effectively modeled by a fusion similarity matrix based on anchor graph while modal correlation can be approximated by Hamming distance. Especially, extracted features from the multi-modal data are classified using deep sparse autoencoders classifier. Finally, experiments conduct on the AD Neuroimaging Initiative database show that DS-FSH outperforms comparable methods of AD classification. To conclude, DS-FSH identifies multi-modal features closely associated with AD, which are expected to contribute significantly to understanding of the pathogenesis of AD.

Integrative transcriptomic and metabolomic analyses reveals the toxicity and mechanistic insights of bioformulated chitosan nanoparticles against Magnaporthe oryzae.

Rice blast, an extremely destructive disease caused by the filamentous fungal pathogen Magnaporthe oryzae, poses a global threat to the production of rice (Oryza sativa L.). The emerging trend of reducing dependence on chemical fungicides for crop protection has increased interest in exploring bioformulated nanomaterials as a sustainable alternative antimicrobial strategy for effectively managing plant diseases. Herein, we used physiomorphological, transcriptomic, and metabolomic methods to investigate the toxicity and molecular action mechanisms of moringa-chitosan nanoparticles (M-CNPs) against M. oryzae. Our results demonstrate that M-CNPs exhibit direct antifungal properties by impeding the growth and conidia formation of M. oryzae in a concentration-dependent manner. Propidium iodide staining indicated concentration-dependent significant apoptosis (91.33%) in the fungus. Ultrastructural observations revealed complete structural damage in fungal cells treated with 200 mg/L M-CNPs, including disruption of the cell wall and destruction of internal organelles. Transcriptomic and metabolomic analyses revealed the intricate mechanism underlying the toxicity of M-CNPs against M. oryzae. The transcriptomics data indicated that exposure to M-CNPs disrupted various processes integral to cell membrane biosynthesis, aflatoxin biosynthesis, transcriptional regulation, and nuclear integrity in M. oryzae., emphasizing the interaction between M-CNPs and fungal cells. Similarly, metabolomic profiling demonstrated that exposure to M-CNPs significantly altered the levels of several key metabolites involved in the integral components of metabolic pathways, microbial metabolism, histidine metabolism, citrate cycle, and lipid and protein metabolism in M. oryzae. Overall, these findings demonstrated the potent antifungal action of M-CNPs, with a remarkable impact at the physiological and molecular level, culminating in substantial apoptotic-like fungal cell death. This research provides a novel perspective on investigating bioformulated nanomaterials as antifungal agents for plant disease control.