ifDEEPre: large protein language-based deep learning enables interpretable and fast predictions of enzyme commission numbers.

Accurate understanding of the biological functions of enzymes is vital for various tasks in both pathologies and industrial biotechnology. However, the existing methods are usually not fast enough and lack explanations on the prediction results, which severely limits their real-world applications. Following our previous work, DEEPre, we propose a new interpretable and fast version (ifDEEPre) by designing novel self-guided attention and incorporating biological knowledge learned via large protein language models to accurately predict the commission numbers of enzymes and confirm their functions. Novel self-guided attention is designed to optimize the unique contributions of representations, automatically detecting key protein motifs to provide meaningful interpretations. Representations learned from raw protein sequences are strictly screened to improve the running speed of the framework, 50 times faster than DEEPre while requiring 12.89 times smaller storage space. Large language modules are incorporated to learn physical properties from hundreds of millions of proteins, extending biological knowledge of the whole network. Extensive experiments indicate that ifDEEPre outperforms all the current methods, achieving more than 14.22% larger F1-score on the NEW dataset. Furthermore, the trained ifDEEPre models accurately capture multi-level protein biological patterns and infer evolutionary trends of enzymes by taking only raw sequences without label information. Meanwhile, ifDEEPre predicts the evolutionary relationships between different yeast sub-species, which are highly consistent with the ground truth. Case studies indicate that ifDEEPre can detect key amino acid motifs, which have important implications for designing novel enzymes. A web server running ifDEEPre is available at https://proj.cse.cuhk.edu.hk/aihlab/ifdeepre/ to provide convenient services to the public. Meanwhile, ifDEEPre is freely available on GitHub at https://github.com/ml4bio/ifDEEPre/.

Deep Learning-Based construction of a Drug-Like compound database and its application in virtual screening of HsDHODH inhibitors.

The process of virtual screening relies heavily on the databases, but it is disadvantageous to conduct virtual screening based on commercial databases with patent-protected compounds, high compound toxicity and side effects. Therefore, this paper utilizes generative recurrent neural networks (RNN) containing long short-term memory (LSTM) cells to learn the properties of drug compounds in the DrugBank, aiming to obtain a new and virtual screening compounds database with drug-like properties. Ultimately, a compounds database consisting of 26,316 compounds is obtained by this method. To evaluate the potential of this compounds database, a series of tests are performed, including chemical space, ADME properties, compound fragmentation, and synthesizability analysis. As a result, it is proved that the database is equipped with good drug-like properties and a relatively new backbone, its potential in virtual screening is further tested. Finally, a series of seedling compounds with completely new backbones are obtained through docking and binding free energy calculations.

Characterization of sucrose nonfermenting-1-related protein kinase 2 (SnRK2) gene family in Haynaldia villosa demonstrated SnRK2.9-V enhances drought and salt stress tolerance of common wheat.

BACKGROUND: The sucrose nonfermenting-1-related protein kinase 2 (SnRK2) plays a crucial role in responses to diverse biotic/abiotic stresses. Currently, there are reports on these genes in Haynaldia villosa, a diploid wild relative of wheat. RESULTS: To understand the evolution of SnRK2-V family genes and their roles in various stress conditions, we performed genome-wide identification of the SnRK2-V gene family in H. villosa. Ten SnRK2-V genes were identified and characterized for their structures, functions and spatial expressions. Analysis of gene exon/intron structure further revealed the presence of evolutionary paths and replication events of SnRK2-V gene family in the H. villosa. In addition, the features of gene structure, the chromosomal location, subcellular localization of the gene family were investigated and the phylogenetic relationship were determined using computational approaches. Analysis of cis-regulatory elements of SnRK2-V gene members revealed their close correlation with different phytohormone signals. The expression profiling revealed that ten SnRK2-V genes expressed at least one tissue (leave, stem, root, or grain), or in response to at least one of the biotic (stripe rust or powdery mildew) or abiotic (drought or salt) stresses. Moreover, SnRK2.9-V was up-regulated in H. villosa under the drought and salt stress and overexpressing of SnRK2.9-V in wheat enhanced drought and salt tolerances via enhancing the genes expression of antioxidant enzymes, revealing a potential value of SnRK2.9-V in wheat improvement for salt tolerance. CONCLUSION: Our present study provides a basic genome-wide overview of SnRK2-V genes in H. villosa and demonstrates the potential use of SnRK2.9-V in enhancing the drought and salt tolerances in common wheat.

Exploring strain-level diversity in the gut microbiome through mucin particle adhesion.

Mucin glycoproteins are a significant source of carbon for the gut bacteria. Various gut microbial species possess diverse hydrolytic enzymes and catabolic pathways for breaking down mucin glycans, resulting in competition for the limited nutrients within the gut environment. Adherence to mucin glycans represents a crucial strategy used by gut microbes to access nutrient reservoirs. Understanding these properties is pivotal for comprehending the survival mechanisms of bacteria in the gastrointestinal tract. However, characterization of individual strains within the vast array of coexisting bacteria in the microbiome is challenging. To investigate this, we developed mucin-immobilized particles by immobilizing porcine gastric mucin (PGM) onto glass beads chemically modified with boronic acid. These PGM-immobilized particles were then anaerobically cultured with human fecal microbiota, and the bacteria adhering to PGM were isolated. Interestingly, the microbiome composition remained largely unchanged irrespective of PGM immobilization. Nonetheless, bacteria isolated from PGM-immobilized glass particles exhibited notably higher N-acetylgalactosaminidase activity compared to the control beads. Furthermore, Bacteroides strains isolated from PGM-immobilized glass particles displayed enhanced adhesive and metabolic properties to PGM. These findings underscore the utility of PGM particles in enriching and isolating specific microbes. Moreover, they highlight substantial differences in microbial properties at the strain level. We anticipate that PGM-immobilized particles will advance culture-based microbiome research, emphasizing the significance of strain-level characterization. IMPORTANCE: Metabolism of mucin glycans by gut bacteria represents a crucial strategy for accessing nutrient reservoirs. The efficacy of mucin glycan utilization among gut bacteria hinges on the metabolic capabilities of individual strains, necessitating meticulous strain-level characterization. In this investigation, we used glass beads chemically immobilized with mucins to selectively enrich bacteria from fecal fermentation cultures, based on their superior adhesion to and metabolism of mucin glycoproteins. These findings lend support to the hypothesis that the physical interactions between bacteria and mucin glycoprotein components directly correlate with their capacity to utilize mucins as nutrient sources. Furthermore, our study implies that physical proximity may significantly influence bacterial nutrient acquisition within the ecosystem, facilitating gut bacteria's access to carbohydrate components.

Identification and genetic characterization of a recently identified enterovirus C116 in China.

Enterovirus C116 (EV-C116) is a new member of the enterovirus C group which is closely associated with several infectious diseases. Although sporadic studies have detected EV-C116 in clinical samples worldwide, there is currently limited information available. In this study, two EV-C-positive fecal specimens were detected in apparently healthy children, which harbored low abundance, through meta-transcriptome sequencing. Based on the prototypes of several EV-Cs, two lineages were observed. Lineage 1 included many types that could not cause EV-like cytopathic effect in cell culture. Three genogroups of EV-C116 were divided in the maximum likelihood tree, and the two strains in this study (XZ2 and XZ113) formed two different lineages, suggesting that EV-C116 still diffuses worldwide. Obvious inter-type recombination events were observed in the XZ2 strain, with CVA22 identified as a minor donor. However, another strain (XZ113) underwent different recombination situations, highlighting the importance of recombination in the formation of EV-Cs biodiversity. The EV-C116 strains could propagate in rhabdomyosarcoma cell cultures at low titer; however, EV-like cytopathic effects were not observed. HEp-2, L20B, VERO, and 293T cell lines did not provide an appropriate environment for EV-C116 growth. These results challenge the traditional recognition of the uncultured nature of EV-C116 strains and explain the difficulty of clinical detection.

Narrow linewidth laser based on a sidewall grating active distributed Bragg reflector.

We demonstrated a narrow linewidth semiconductor laser based on a deep-etched sidewall grating active distributed Bragg reflector (SG-ADBR). The coupling coefficients and reflectance were numerically simulated for deep-etched fifth-order SG-ADBR, and a reflectance of 0.86 with a bandwidth of 1.04 nm was obtained by the finite element method for a 500-period SG-ADBR. Then the fifth-order SG-ADBR lasers were fabricated using projection i-line lithography processes. Single-mode lasing at 1537.9 nm was obtained with a high side-mode suppression ratio (SMSR) of 65 dB, and a continuous tuning range of 10.3 nm was verified with SMSRs greater than 53 dB. Furthermore, the frequency noise power spectral density was characterized, from which a Lorentzian linewidth of 288 kHz was obtained.

Directly modulated deformed-square-FP coupled-cavity laser with intracavity-mode photon-photon resonance.

We propose and demonstrate a high-speed directly modulated laser based on a hybrid deformed-square-FP coupled cavity (DFC), aiming for a compact-size low-cost light source in next-generation optical communication systems. The deformed square microcavity is directly connected to the FP cavity and utilized as a wavelength-sensitive reflector with a comb-like and narrow-peak reflection spectrum for selecting the lasing mode, which can greatly improve the single-mode yield of the laser and the quality (Q) factor of the coupled mode. By optimizing the device design and operating condition, the modulation bandwidth of the DFC laser can be enhanced due to the intracavity-mode photon-photon resonance effect. Our experimental results show an enhancement of 3-dB modulation bandwidth from 19.3 GHz to 30 GHz and a clear eye diagram at a modulation rate of 25 Gbps.

Feedback insensitivity in a self-chaotic microcavity laser.

Insensitivity to external optical feedback is experimentally demonstrated in a self-chaotic deformed square microcavity laser for the first time, to the best of our knowledge. Both the optical and radio frequency (RF) spectra of the microlaser remain unaffected for external optical feedback with feedback strength as high as 9.9 dB. In addition, the autocorrelation function curve exhibits no time-delayed peaks. The insensitivity makes the self-chaotic microcavity laser promising for applications in feedback-insensitive optical sources.

Strain-Amplified Exciton Chirality in Organic-Inorganic Hybrid Materials.

Chiral organic-inorganic hybrids combining chirality of organic molecules and semiconducting properties of inorganic frameworks generate chiral excitons without external spin injection, creating the potential for chiroptoelectronics. However, the relationship between molecular chirality and exciton chirality is still unclear. Here we show the strain-amplified exciton chirality in one-dimensional chiral metal halides. Utilizing chirality-induced spin-orbital coupling theory, we quantitatively demonstrate the impact of the strain-engineered molecular assembly of chiral cations on exciton chirality, offering a feasible way to amplify exciton chirality by molecular manipulation.

Design Strategies toward High-Utilization Zinc Anodes for Practical Zinc-Metal Batteries.

Aqueous Zn-metal batteries (AZMBs) hold a promise as the next-generation energy storage devices due to their low cost and high specific energy. However, the actual energy density falls far below the requirements of commercial AZMBs due to the use of excessive Zn as anode and the associated issues including dendritic growth and side reactions. Reducing the N/P ratio (negative capacity/positive capacity) is an effective approach to achieve high energy density. A significant amount of research has been devoted to increasing the cathode loading and specific capacity or tuning the Zn anode utilization to achieve low N/P ratio batteries. Nevertheless, there is currently a lack of comprehensive overview regarding how to enhance the utilization of the Zn anode to balance the cycle life and energy density of AZMBs. In this review, we summarize the challenges faced in achieving high-utilization Zn anodes and elaborate on the modifying strategies for the Zn anode to lower the N/P ratio. The current research status and future prospects for the practical application of high-performance AZMBs are proposed at the end of the review.

Genetic Underpinnings of Cuticular Hydrocarbon Biosynthesis in the German Cockroach, Blattella germanica (L.): Progress and Perspectives.

Insect cuticular hydrocarbons (CHCs) serve as important waterproofing barriers and as signals and cues in chemical communication. Over the past 30 years, numerous studies on CHCs have been conducted in the German cockroach, Blattella germanica, leading to substantial progress in the field. However, there has not been a systematic review of CHC studies in this species in recent years. This review aims to provide a concise overview of the chemical composition, storage, transport, and physical properties of different CHCs in B. germanica. Additionally, we focus on the biosynthetic pathway and the genetic regulation of HC biosynthesis in this species. A considerable amount of biochemical evidence regarding the biosynthetic pathway of insect CHCs has been gathered from studies conducted in B. germanica. In recent years, there has also been an improved understanding of the molecular mechanisms that underlie CHC production in this insect. In this article, we summarize the biosynthesis of different classes of CHCs in B. germanica. Then, we review CHCs reaction to various environmental conditions and stressors and internal physiological states. Additionally, we review a body of work showing that in B. germanica, CHC profiles exhibit significant sexual dimorphism, specific CHCs act as essential precursors for female contact sex pheromone components, and we summarize the molecular regulatory mechanisms that underlie sexual dimorphism of CHC profiles. Finally, we highlight future directions and challenges in research on the biosynthesis and regulatory mechanisms of CHCs in B. germanica, and also identify potential applications of CHC studies in the pest control.

Potential environmental and human health menace of spent graphite in lithium-ion batteries.

The growing demand for lithium-ion batteries for portable electronics and electric vehicles results in a booming lithium battery market, leading to a concomitant increase in spent graphite. This research investigated the potential impacts of spent graphite on environmental and human health using standardized toxicity extraction and Life Cycle Impact Assessment models. The spent graphite samples were classified as hazardous waste due to the average nickel content of 337.14 mg/L according to Chinese regulations. Besides, cadmium and fluorine were the other elements that exceeded the regulations threshold. Easily ignored aluminum and heavy metal cobalt are other harmful elements according to the results of Life Cycle Impact Assessments. All the metallic harmful elements mainly exist in a transferable state. Thermogravimetry infrared spectrometry coupled with mass spectrometry was employed to recognize the emitted gases and explore gas emission behavior. Inorganic gases of CO, H2S, SO2, SO3, oxynitride, HCl, and fluoride-containing gases were detected. Sulfur-containing gases released from spent graphite were contributed by the residual sulfuric acid after leaching. The correlation between the evolution of emitted gases and the heating schedule was established simultaneously. The research comprehensively illustrates the pollution of spent graphite and provides assistance for the design of green recycling schemes for spent graphite.

UiO-66 nanoparticles combat influenza A virus in mice by activating the RIG-I-like receptor signaling pathway.

The Influenza A virus (IAV) is a zoonotic pathogen that infects humans and various animal species. Infection with IAV can cause fever, anorexia, and dyspnea and is often accompanied by pneumonia characterized by an excessive release of cytokines (i.e., cytokine storm). Nanodrug delivery systems and nanoparticles are a novel approach to address IAV infections. Herein, UiO-66 nanoparticles (NPs) are synthesized using a high-temperature melting reaction. The in vitro and in vivo optimal concentrations of UiO-66 NPs for antiviral activity are 200 µg mL-1 and 60 mg kg-1, respectively. Transcriptome analysis revealed that UiO-66 NPs can activate the RIG-I-like receptor signaling pathway, thereby enhancing the downstream type I interferon antiviral effect. These NPs suppress inflammation-related pathways, including the FOXO, HIF, and AMPK signaling pathways. The inhibitory effect of UiO-66 NPs on the adsorption and entry of IAV into A549 cells is significant. This study presents novel findings that demonstrate the effective inhibition of IAV adsorption and entry into cells via UiO-66 NPs and highlights their ability to activate the cellular RIG-I-like receptor signaling pathway, thereby exerting an anti-IAV effect in vitro or in mice. These results provide valuable insights into the mechanism of action of UiO-66 NPs against IAV and substantial data for advancing innovative antiviral nanomedicine.

Optical time domain reflectometry based on a self-chaotic circular-sided microcavity laser.

A self-chaotic circular-sided square microcavity laser, with a chaos bandwidth of 12.9 GHz and a flatness of ±3d B, was applied in optical time domain reflectometry (OTDR). Using the broadband chaos laser, we demonstrated a range resolution of 4.5 mm and a 25-km detection distance experimentally. The solitary wide-bandwidth microcavity chaos laser, without the extra correlation peaks in optical feedback chaotic lasers, has shown potential advantages for correlation OTDR in practical application.

Effects of glutaraldehyde and povidone-iodine on apoptosis of grass carp liver and hepatocytes.

Since disinfectants are used all over the world to treat illnesses in people and other animals, they pose a major risk to human health. The comprehensive effects of disinfectant treatments on fish liver, especially the impacts on oxidative stress, toxicological effects, transcriptome profiles, and apoptosis, have not yet been fully analyzed. In the current investigation, healthy grass carp were exposed to 80 µg/L glutaraldehyde or 50 µg/L povidone-iodine for 30 days. First, the findings of enzyme activity tests demonstrated that the administration of glutaraldehyde could considerably increase oxidative stress by lowering T-SOD, CAT, and GPx and raising MDA. Furthermore, KEGG research revealed that exposure to glutaraldehyde and povidone-iodine stimulated the PPAR signal pathway. To further elucidate the transcriptome results, the relative expressions of related DEGs in the PPAR signal pathway were verified. Glutaraldehyde induced apoptosis in liver tissue of grass carp; however, it activated cytotoxicity and apoptosis in grass carp hepatocytes when exposed to glutaraldehyde or povidone-iodine. According to the current study, disinfectants can cause the impairment of the immune system, oxidative stress, and attenuation of the PPAR signal pathway in the liver of grass carp, making them detrimental as dietary supplements for grass carp, particularly in the aquaculture sector.

Evaluation of the efficacy and quality of life in patients with temporomandibular joint disorders treated with Kovacs digital occlusal splint: a pilot study.

BACKGROUND: Few studies have been conducted on treating temporomandibular disorders (TMDs) with new digital occlusal splints, which has increasingly attracted wide attention. METHODS: To evaluate the clinical efficacy and quality of life (QoL) of Kovacs digital occlusal splint (KDOS) treatment in patients with TMD. MATERIALS AND METHODS: Eighty-nine patients with TMD who were treated using KDOS were analyzed. The patients were divided into three groups according to the Wilkes stage. The clinical symptoms and QoL scores of the patients in each group were recorded before and at least three months after treatment, and the data were statistically analyzed and compared. The relationships between the disease severity, sex, age, and level of QoL before treatment and improvement in the clinical symptoms were analyzed using binary logistic regression. RESULTS: The mean age and follow-up period of the patients were 28.0 ± 10.4 years and 4.9 ± 2.1 months, respectively. After KDOS treatment, the improvement rates of joint noise and pain were 80.4% and 69.8%, respectively. Additionally, the patients' maximum mouth opening and global QoL mean scores significantly improved compared to those before treatment (p < 0.001). Binary logistic regression analysis revealed that the factors affecting the improvement in the clinical symptoms were disease severity and level of QoL before treatment. CONCLUSIONS: KDOS can improve the clinical symptoms and QoL of patients with TMD. Moreover, patients without osteoarthritis and with low pretreatment QoL levels are more likely to demonstrate clinical improvement. TRIAL REGISTRATION: The trial was registered with Chinese Clinical Trial Registry (ChiCTR) (ID: ChiCTR2300076518) on 11/10/2023.

[Oblique Lumbar Interbody Fusion Combined With 4-Screw Fixation for Treating Two-Level Degenerative Lumbar Diseases:A Finite Element Study].

Objective To demonstrate the feasibility of oblique lumbar interbody fusion (OLIF) combined with 4-screw fixation for treating two-level lumbar degenerative diseases.Methods An intact finite element model of L3-S1 (M0) was constructed and validated.Then,we constructed the M1 model by simulating OLIF surgery at L3/4 and L4/5 segments on the M0 model.By attachment of posterior 4-screw or 6-screw fixation to the M1 model,three 4-screw fixation models (M2-M4) and one 6-screw fixation model (M5) were established.The segmental and overall range of motion (ROM) and the peak von Mises stresses of superior endplate,cage,and posterior screw-rod were investigated under each implanted condition.Results Under the motion modes of forward flexion,backward extension,bilateral (left and right) flexion,and left and right rotation,the L3/4 ROM of M2 model and L4/5 ROM of M3 model increased,while the L3/4 and L4/5 ROM of M4 and M5 models significantly decreased compared with those of M1 model.Under all motion modes,the L4 superior endplate in M2 model and the L5 superior endplate in M3 model showed the maximum peak von Mises stress,and the peak von Mises stresses of L4 and L5 superior endplates in M4 and M5 models were close.The L3/4 cage in M2 model and the L4/5 cage in M3 model showcased the largest peak von Mises stress,and the peak von Mises stresses of cages in M4 and M5 models were close.The peak stresses of internal fixation in M2-M5 models were close.Conclusion Four-screw fixation can replace 6-screw fixation in the OLIF surgery for treating two-level degenerative lumbar diseases.

A Single Set of Well-Designed Aptamer Probes for Reliable On-site Qualitative and Ultra-Sensitive Quantitative Detection.

Aptamer-based probes are pivotal components in various sensing strategies, owing to their exceptional specificity and versatile programmable structure. Nevertheless, numerous aptamer-based probes usually offer only a single function, limiting their capacity to meet the diverse requirements of multi-faceted sensing systems. Here, we introduced supersandwich DNA probes (SSW-DNA), designed and modified on the outer surface of nanochannels with hydrophobic inner walls, enabling dual functionality: qualitative detection for on-site analysis and quantitative detection for precise analysis. The fragmented DNAs resulting from the target recognition, are subsequently identified through lateral flow assays, enabling robust on-site qualitative detection of microcystin-LR with an impressively low limit of detection (LOD) at 0.01 µg/L. Meanwhile, the nanochannels enable highly sensitive quantification of microcystin-LR through the current analysis, achieving an exceptionally low LOD at 2.5×10-7  µg/L, with a broad dynamic range spanning from 1×10-6 to 1×102  µg/L. Furthermore, the process of target recognition introduces just a single potential error propagation, which reduces the overall risk of errors during the entire qualitative and quantitative detection process. This sensing strategy broadens the scope of applications for aptamer-based composite probes, holding promising implications across diverse fields, such as medical diagnosis, food safety, and environmental protection.

[Determination of plasma protein binding rate of Shuganning Injection using equilibrium dialysis and UPLC-MS/MS].

Traditional Chinese medicine(TCM) compound preparations have complex compositions. As a widely used TCM injection, Shuganning Injection, its in vivo processes are not yet fully understood. Determining the plasma protein binding rate is of great significance for pharmacokinetic and pharmacodynamic studies. In this experiment, the equilibrium dialysis method combined with UPLC-MS/MS technology was used to determine the plasma protein binding rates of 10 components, including p-hydroxyacetophenone, caffeic acid, baicalein, oroxylin A, geniposide, baicalin, cynaroside, oroxylin A-7-O-ß-D-glucuronide, scutellarin, and hyperoside, in Shuganning Injection in rat and human plasma to provide a theoretical basis for further elucidating the in vivo processes of Shuganning Injection and guiding clinical medication. The results showed that, except for baicalein and geniposide, the plasma protein binding rates of the other eight components were higher in human plasma than in rat plasma, and there were interspecies differences. In human plasma, except for geniposide, caffeic acid, and baicalin, the plasma protein binding rates of the remaining seven components were above 80%, with baicalein and oroxylin A exceeding 90%. All components exhibit a high level of binding to plasma proteins, with the exception of geniposide.