Deep learning for multi-type infectious keratitis diagnosis: A nationwide, cross-sectional, multicenter study.

The main cause of corneal blindness worldwide is keratitis, especially the infectious form caused by bacteria, fungi, viruses, and Acanthamoeba. The key to effective management of infectious keratitis hinges on prompt and precise diagnosis. Nevertheless, the current gold standard, such as cultures of corneal scrapings, remains time-consuming and frequently yields false-negative results. Here, using 23,055 slit-lamp images collected from 12 clinical centers nationwide, this study constructed a clinically feasible deep learning system, DeepIK, that could emulate the diagnostic process of a human expert to identify and differentiate bacterial, fungal, viral, amebic, and noninfectious keratitis. DeepIK exhibited remarkable performance in internal, external, and prospective datasets (all areas under the receiver operating characteristic curves > 0.96) and outperformed three other state-of-the-art algorithms (DenseNet121, InceptionResNetV2, and Swin-Transformer). Our study indicates that DeepIK possesses the capability to assist ophthalmologists in accurately and swiftly identifying various infectious keratitis types from slit-lamp images, thereby facilitating timely and targeted treatment.

Trace elements in pancreatic cancer.

BACKGROUND: Pancreatic cancer (PCA) is an extremely aggressive malignant cancer with an increasing incidence and a low five-year survival rate. The main reason for this high mortality is that most patients are diagnosed with PCA at an advanced stage, missing early treatment options and opportunities. As important nutrients of the human body, trace elements play an important role in maintaining normal physiological functions. Moreover, trace elements are closely related to many diseases, including PCA. REVIEW: This review systematically summarizes the latest research progress on selenium, copper, arsenic, and manganese in PCA, elucidates their application in PCA, and provides a new reference for the prevention, diagnosis and treatment of PCA. CONCLUSION: Trace elements such as selenium, copper, arsenic and manganese are playing an important role in the risk, pathogenesis, diagnosis and treatment of PCA. Meanwhile, they have a certain inhibitory effect on PCA, the mechanism mainly includes: promoting ferroptosis, inducing apoptosis, inhibiting metastasis, and inhibiting excessive proliferation.

All-fiber multifunction differential absorption CO2 lidar integrating single-photon and coherent detection.

This study demonstrates a differential absorption lidar (DIAL) for CO2 that integrates both single-photon direct detection and coherent detection. Based on all-fiber 1572 nm wavelength devices, this compact lidar achieves detection of CO2 concentration, wind field, and single photon aerosol backscattering signal. First, by comparing DIAL with VAISALA-GMP343, the concentration deviation between the two devices is less than 5 ppm, proving the accuracy of the DIAL. Second, through the scanning detection experiment in Chaohu Lake, Hefei, not only the CO2 concentration between single-photon detection and coherent detection but also the wind field was obtained, proving the multifunctionality and stability of the DIAL. Benefiting from the advantages of combined the two detection methods, single photon detection offers 3-km CO2 and aerosol backscattering signals; coherent detection offers a 360-m shorter blind zone and wind field. This DIAL can achieve monitoring of CO2 flux and sudden emissions, which can effectively compensate for the shortages of in-situ sensors and spaceborne systems.

Storage-D: A user-friendly platform that enables practical and personalized DNA data storage.

Deoxyribonucleic acid (DNA) has been suggested as a very promising medium for data storage in recent years. Although numerous studies have advocated for DNA data storage, its practical application remains obscure and there is a lack of a user-oriented platform. Here, we developed a DNA data storage platform, named Storage-D, which allows users to convert their data into DNA sequences of any length and vice versa by selecting algorithms, error-correction, random-access, and codec pin strategies in terms of their own choice. It incorporates a newly designed "Wukong" algorithm, which provides over 20 trillion codec pins for data privacy use. This algorithm can also control GC content to the selected standard, as well as adjust the homopolymer run length to a defined level, while maintaining a high coding potential of ~1.98 bis/nt, allowing it to outperform previous algorithms. By connecting to a commercial DNA synthesis and sequencing platform with "Storage-D," we successfully stored "Diagnosis and treatment protocol for COVID-19 patients" into 200 nt oligo pools in vitro, and 500 bp genes in vivo which replicated in both normal and extreme bacteria. Together, this platform allows for practical and personalized DNA data storage, potentially with a wide range of applications.

Modulation of Lipid Dynamics in the ß-Amyloid Aggregates Induced Membrane Fragmentation.

Nonspecific membrane disruption is considered a plausible mechanism for the cytotoxicity induced by ß-amyloid (Aß) aggregates. In scenarios of high local Aß concentrations, a two-step membrane fragmentation model has been proposed. Initially, membrane-embedded Aß oligomeric aggregates form, followed by membrane fragmentation. However, the key molecular-level interactions between Aß oligomeric aggregates and lipids that drive the second-stage membrane fragmentation remain unclear. This study monitors the time-dependent changes in lipid dynamics and water accessibility of model liposomes during Aß-induced membrane fragmentation. Our results indicate that lipid dynamics on the nanosecond to microsecond time scale undergo rapid acceleration upon initial incubation with membrane-incorporated Aß oligomeric aggregates, followed by a slow deceleration process. Concurrently, lipid headgroups become less accessible to water. Both observations suggest a carpet-like mechanism of membrane disruption for the Aß-induced membrane fragmentation process.

Neutron spin echo shows pHLIP is capable of retarding membrane thickness fluctuations.

Cell membranes are responsible for a range of biological processes that require interactions between lipids and proteins. While the effects of lipids on proteins are becoming better understood, our knowledge of how protein conformational changes influence membrane dynamics remains rudimentary. Here, we performed experiments and computer simulations to study the dynamic response of a lipid membrane to changes in the conformational state of pH-low insertion peptide (pHLIP), which transitions from a surface-associated (SA) state at neutral or basic pH to a transmembrane (TM) α-helix under acidic conditions. Our results show that TM-pHLIP significantly slows down membrane thickness fluctuations due to an increase in effective membrane viscosity. Our findings suggest a possible membrane regulatory mechanism, where the TM helix affects lipid chain conformations, and subsequently alters membrane fluctuations and viscosity.

Plant-derived extracellular vesicles as a promising anti-tumor approach: A comprehensive assessment of effectiveness, safety, and mechanisms.

BACKGROUND: Plant-derived extracellular vesicles (PDEs) are expected to be a compelling alternative for cancer treatment due to their low cytotoxicity, low immunogenicity, high yield, and potential anti-tumor efficacy. Despite the significant advantages of PDEs, the reliable evidence for PDEs as promising anti-tumor approach remains unsystematic and insufficient. Some challenges remain for the clinical application and large-scale industrial production of PDEs. PURPOSE: Through systematic evaluation and meta-analysis, the objective was to provide scientific, systematic and reliable preclinical evidence to support the clinical use of PDEs in cancer therapy. METHODS: The search for relevant literature, conducted up to March 2024, encompassed various databases including Web of Science, the Cochrane Library, Embase, PubMed, CNKI, Wanfang Data, and the China Science and Technology Journal Database. The SYRCLE´s risk of bias tool was used to assess the methodological quality of the animal studies. For overall effect analysis and subgroup analysis, RevMan 5.4 and Stata 12.0 were utilized. RESULTS: The analysis incorporated a total of 38 articles, comprising 29 in vivo studies and 9 in vitro studies. Meta-analysis indicated that PDEs significantly reduced cancer cell activity and induced apoptosis, reduced tumor volume and tumor weight when used as therapeutic agents, as well as exhibited synergistic anti-cancer via combination therapy. Additionally, PDEs-drugs exerted stronger inhibition of tumor volume compared to the free drug or commercial liposome-drugs. Their therapeutic effects were closely related to regulating tumor cell biological behavior and remodeling the tumor microenvironment. The safety was associated with administration route of PDEs, oral administration was currently preferred until more in-depth studies on the safety of other methods are conducted. CONCLUSIONS: The meta-analysis revealed that PDEs have systematic and reliable preclinical evidence in preclinical studies of cancer therapy, and their efficacy and certain safety could support the clinical application of PDEs in cancer therapy. Of course, further researches are required for large-scale industrial production to meet the needs of clinical applications.

Decoupled response of microbial taxa and functions to nutrients: The role of stoichiometry in plantations.

The resource quantity and elemental stoichiometry play pivotal roles in shaping belowground biodiversity. However, a significant knowledge gap remains regarding the influence of different plant communities established through monoculture plantations on soil fungi and bacteria's taxonomic and functional dynamics. This study aimed to elucidate the mechanisms underlying the regulation and adaptation of microbial communities at the taxonomic and functional levels in response to communities formed over 34 years through monoculture plantations of coniferous species (Japanese larch, Armand pine, and Chinese pine), deciduous forest species (Katsura), and natural shrubland species (Asian hazel and Liaotung oak) in the temperate climate. The taxonomic and functional classifications of fungi and bacteria were examined for the mineral topsoil (0-10 cm) using MiSeq-sequencing and annotation tools of microorganisms (FAPROTAX and Funguild). Soil bacterial (6.52 ± 0.15) and fungal (4.46 ± 0.12) OTUs' diversity and richness (5.83*103±100 and 1.12*103±46.4, respectively) were higher in the Katsura plantation compared to Armand pine and Chinese pine. This difference was attributed to low soil DOC/OP (24) and DON/OP (11) ratios in the Katsura, indicating that phosphorus availability increased microbial community diversity. The Chinese pine plantation exhibited low functional diversity (3.34 ± 0.04) and richness (45.2 ± 0.41) in bacterial and fungal communities (diversity 3.16 ± 0.15 and richness 56.8 ± 3.13), which could be attributed to the high C/N ratio (25) of litter. These findings suggested that ecological stoichiometry, such as of enzyme, litter C/N, soil DOC/DOP, and DON/DOP ratios, was a sign of the decoupling of soil microorganisms at the genetic and functional levels to land restoration by plantations. It was found that the stoichiometric ratios of plant biomass served as indicators of microbial functions, whereas the stoichiometric ratios of available nutrients in soil regulated microbial genetic diversity. Therefore, nutrient stoichiometry could serve as a strong predictor of microbial diversity and composition during forest restoration.

"Cell Disk" DNA Storage System Capable of Random Reading and Rewriting.

DNA has emerged as an appealing material for information storage due to its great storage density and durability. Random reading and rewriting are essential tasks for practical large-scale data storage. However, they are currently difficult to implement simultaneously in a single DNA-based storage system, strongly limiting their practicability. Here, a "Cell Disk" storage system is presented, achieving high-density in vivo DNA data storage that enables both random reading and rewriting. In this system, each yeast cell is used as a chamber to store information, similar to a "disk block" but with the ability to self-replicate. Specifically, each genome of yeast cell has a customized CRISPR/Cas9-based "lock-and-key" module inserted, which allows selective retrieval, erasure, or rewriting of the targeted cell "block" from a pool of cells ("disk"). Additionally, a codec algorithm with lossless compression ability is developed to improve the information density of each cell "block". As a proof of concept, target-specific reading and rewriting of the compressed data from a mimic cell "disk" comprising up to 105 "blocks" are demonstrated and achieve high specificity and reliability. The "Cell Disk" system described here concurrently supports random reading and rewriting, and it should have great scalability for practical data storage use.

Palladium-Catalyzed Carbonylation Reaction of Indole/Pyrrole Involving HCFO-1233zd (E).

3-Indole-3-one is a key intermediate in the synthesis of many drugs and plays an important role in synthetic chemistry and biochemistry. A new method for synthesizing trifluoromethylated 3-indoleketones by Pd(0)-catalyzed carbonylation was introduced. In the absence of additives, 1-chloro-3,3,3-trifluoropropyl (an inexpensive and environmentally friendly synthetic block of trifluoromethyl) reacts with indole and carbon monoxide to generate trifluoromethylindole ketones with good yields, regioselectivity, and chemical selectivity; furthermore, the products exhibit strong resistance to basic functional groups, such as alkynes, aldehydes, and esters. In addition to the conversion of indole compounds into corresponding products, pyrrole and heteroindole may be suitable for corresponding chemical transformations. This study provides a synthetic method for the further construction of trifluoromethylated 3-indole ketones.

A Green Asymmetric Bicyclic Co-Solvent Molecule for High-Voltage Aqueous Lithium-Ion Batteries.

Hybridizing aqueous electrolytes with organic co-solvents can effectively expand the voltage window of aqueous electrolytes while reducing salt usage, but most reported co-solvents are usually flammable and toxic, hardly achieving compatibility between safety and electrochemical performance. Here, a new non-flammable and non-toxic low-salt-concentration (1.85 m) aqueous electrolyte is reported using the green co-solvent isosorbide dimethyl ether (IDE). Owing to its unique 3D molecular structure, IDE can form a five-membered ring structure by binding the Li ion. The steric hindrance effect from IDE weakens its solvation ability, generating anion-participated solvation structures that produce a robust and uniform LiF-rich solid electrolyte interphase layer while containing elastic IDE-derived organics. Moreover, the multiple O atoms in IDE can effectively regulate the intermolecular hydrogen bonding networks, reducing H2O molecule activity and expanding the electrochemical window. Such unique solvation structures and optimized hydrogen bonding networks enabled by IDE effectively suppress electrode/electrolyte interfacial side reactions, achieving a 4.3 V voltage window. The as-developed Li4Ti5O12(LTO)||LiMn2O4(LMO) full cell delivers outstanding cycling performance over 450 cycles at 2 C. The proposed green hybrid aqueous electrolyte provides a new pathway for developing high-voltage aqueous lithium batteries.

Rigidifying of the internal dynamics of amyloid-beta fibrils generated in the presence of synaptic plasma vesicles.

We investigated the changes in internal flexibility of amyloid-ß1-40 (Aß) fibrils grown in the presence of rat synaptic plasma vesicles. The fibrils are produced using a modified seeded growth protocol, in which the Aß concentration is progressively increased at the expense of the decreased lipid to protein ratio. The morphologies of each generation are carefully assessed at several fibrils' growth time points using transmission electron microscopy. The side-chain dynamics in the fibrils is investigated using deuterium solid-state NMR measurements, with techniques spanning line shapes analysis and several NMR relaxation rates measurements. The dynamics is probed in the site-specific fashion in the hydrophobic C-terminal domain and the disordered N-terminal domain. An overall strong rigidifying effect is observed in comparison with the wild-type fibrils generated in the absence of the membranes. In particular, the overall large-scale fluctuations of the N-terminal domain are significantly reduced, and the activation energies of rotameric inter-conversion in methyl-bearing side-chains of the core (L17, L34, M35, V36), as well as the ring-flipping motions of F19 are increased, indicating a restricted core environment. Membrane-induced flexibility changes in Aß aggregates can be important for the re-alignment of protein aggregates within the membrane, which in turn would act as a disruption pathway of the bilayers' integrity.

The temporal progression of retinal degeneration and early-stage idebenone treatment in the Pde6brd1/rd1 mouse model of retinal dystrophy.

Photoreceptor cell death, primarily through apoptosis, related to retinal disorders like retinitis pigmentosa (RP), would result in vision loss. The pathological processes and crucial mutant conditions preceding photoreceptor cell demise are not well understood. This study aims to conduct an in-depth examination of early-stage changes in the widely utilized Pde6brd1/rd1 (rd1) mouse model, which has Pde6b gene mutations representing autosomal recessive RP disorder. We investigated the morphology and ultrastructure of retinal cells, including second-order neurons, during the initial phase of disease progression. Our findings revealed that mitochondrial alterations in rod photoreceptors were present as a predeath mutant state as early as postnatal day 3 (P3). The bipolar and horizontal cells from the rd1 mouse retina exhibited significant morphological changes in response to loss of photoreceptor cells, indicating that second-order neurons rely on these cells for their structures. Subsequent oral administration of idebenone, a mitochondria-protective agent, enhanced retinal function and promoted both photoreceptor cell survival and inner retinal second-order synaptogenesis in rd1 mice at P14. Our findings offer a mechanistic framework, suggesting that mitochondrial damage acts as an early driver for photoreceptor cell death in retinal degeneration.

Use of solid thermolytic salts to facilitate microwave-induced in situ amorphization.

Moisture was frequently used as dielectric heating source in classical microwave-able systems to facilitate microwave-induced in situ amorphization, however such systems may face the potential of drug hydrolysis. In this study, solid thermolytic salts were proposed to function as moisture substitutes and their feasibility and impacts on microwave-induced in situ amorphization were investigated. It was found that NH4HCO3 was a promising solid alkaline salt to facilitate both microwave-induced in situ amorphization and in situ salt formation of acidic indomethacin (IND). Moreover, it could improve the chemical stability of the drug and the dissolution performance of compacts relative to classical moisture-based compacts upon microwaving. Further mechanistic study suggested that the in situ amorphization occurred prior to the in situ salt formation, especially in formulations with low drug loadings and high solid salt mass ratios. For compacts with low polymer ratios, in situ salt formation took place subsequently, where the previously amorphized IND within compacts could interact with the NH3 gas produced in situ by the decomposition of NH4HCO3 and form the ammonium IND salt. Microwaving time showed great impacts on the decomposition of NH4HCO3 and the in situ generation of water and NH3, which indirectly affected the amorphization and salt formation of IND. In comparison to the moisture-based systems, the NH4HCO3-based system showed a number of advantages, including the reduced potential of IND hydrolysis due to the absence of absorbed moisture, a wider category of applicable polymeric carriers other than hygroscopic polymers, and an increase in drug loading up to 50% (w/w).

NH2-MIL-125-Derived N-Doped TiO2@C Visible Light Catalyst for Wastewater Treatment.

The utilization of titanium dioxide (TiO2) as a photocatalyst for the treatment of wastewater has attracted significant attention in the environmental field. Herein, we prepared an NH2-MIL-125-derived N-doped TiO2@C Visible Light Catalyst through an in situ calcination method. The nitrogen element in the organic connector was released through calcination, simultaneously doping into the sample, thereby enhancing its spectral response to cover the visible region. The as-prepared N-doped TiO2@C catalyst exhibited a preserved cage structure even after calcination, thereby alleviating the optical shielding effect and further augmenting its photocatalytic performance by increasing the reaction sites between the catalyst and pollutants. The calcination time of the N-doped TiO2@C-450 °C catalyst was optimized to achieve a balance between the TiO2 content and nitrogen doping level, ensuring efficient degradation rates for basic fuchsin (99.7%), Rhodamine B (89.9%) and tetracycline hydrochloride (93%) within 90 min. Thus, this study presents a feasible strategy for the efficient degradation of pollutants under visible light.

Cell softness reveals tumorigenic potential via ITGB8/AKT/glycolysis signaling in a mice model of orthotopic bladder cancer / 中华医学杂志(英文版)

BACKGROUND@#Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a micro-barrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.@*METHODS@#The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models.@*RESULTS@#Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.@*CONCLUSIONS@#The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Nitrogen deposition raises temperature sensitivity of soil organic matter decomposition in subtropical forest.

Subtropical ecosystems are strongly affected by nitrogen (N) deposition, impacting soil organic matter (SOM) availability and stocks. Here we aimed to reveal the effects of N deposition on i) the structure and functioning of microbial communities and ii) the temperature sensitivity (Q10) of SOM decomposition. Phosphorus (P) limited evergreen forest in Guangdong Province, southeastern China, was selected, and N deposition (factor level: N (100 kg N ha-1 y-1 (NH4NO3)) and control (water), arranged into randomized complete block design (n = 3)) was performed during 2.5 y. After that soils from 0 to 20 cm were collected, analyzed for the set of parameters and incubated at 15, and 25, and 35 °C for 112 days. N deposition increased the microbial biomass N and the content of fungal and Gram-positive bacterial biomarkers; activities of beta-glucosidase (BG) and acid phosphatase (ACP) also increased showing the intensification of SOM decomposition. The Q10 of SOM decomposition under N deposition was 1.66 and increased by 1.4 times than under control. Xylosidase (BX), BG, and ACP activities increased with temperature under N but decreased with the incubation duration, indicating either low production and/or decomposition of enzymes. Activities of polyphenol-(PPO) and peroxidases (POD) were higher under N than in the control soil and were constant during the incubation showing the intensification of recalcitrant SOM decomposition. At the early incubation stage (10 days), the increase of Q10 of CO2 efflux was explained by the activities of BX, BQ, ACP, and POD and the quality of the available dissolved organic matter pool. At the later incubation stages (112 days), the drop of Q10 of CO2 efflux was due to the depletion of the labile organic substances and the shift of microbial community structure to K-strategists. Thus, N deposition decoupled the effects of extracellular enzyme activities from microbial community structure on Q10 of SOM decomposition in the subtropical forest soil.

Heterotypic Interactions between the 40- and 42-Residue Isoforms of ß-Amyloid Peptides on Lipid Bilayer Surfaces.

Co-aggregation involving different amyloidogenic sequences has been emphasized recently in the modified amyloid cascade hypothesis. Yet, molecular-level interactions between two predominant ß-amyloid peptide sequences, Aß40 and Aß42, in the fibrillation process in membrane-mimicked environments remain unclear. Here, we report biophysical evidence that demonstrates the molecular-level interactions between Aß40 and Aß42 at the membrane-associated conucleation stage using dynamic nuclear polarization-enhanced solid-state NMR spectroscopy. These residue-specific contacts are distinguished from those reported in mature fibrils formed by either Aß40 or Aß42. Meanwhile, site-specific interactions between Aß and lipid molecules and modulation of microsecond-time-scale lipid dynamics are observed, which may be responsible for the more rapid and significant membrane content leakage compared to that with Aß40 alone.

Co-delivery of minoxidil and tocopherol acetate ethosomes to reshape the hair Follicular Microenvironment and promote hair regeneration in androgenetic alopecia.

The most prevalent kind of hair loss is androgenic alopecia (AGA), which is characterized by hair follicle miniaturization and microenvironment dysfunction. Although topical Minoxidil (MXD) was considered to be a safe and effective treatment for AGA, excess reactive oxygen species (ROS) and lower sulfotransferase activity in the hair follicular microenvironment led to an unsatisfactory treatment of AGA. Here, we developed the ethosome (MTE) load of minoxidil and tocopherol acetate to improve the therapeutic effect of MXD on androgenic alopecia. It could regulate the microenvironment around hair follicles, promote the telogen-to-anagen transition of hair follicles, and boost hair regeneration, thus achieving a synergistic effect of 1 + 1 > 2. The results proved that MTE showed excellent stability, biosafety, and good dermal and follicular permeability in vitro. The hair regeneration ability of AGA model mice showed that the co-delivery ethosome might regulate the microenvironment around the hair follicles and improve hair regeneration in comparison to the commercial minoxidil tincture alone. As a result, the strategy provided a promising new strategy for the treatment of AGA.