A comprehensive computational benchmark for evaluating deep learning-based protein function prediction approaches.

Proteins play an important role in life activities and are the basic units for performing functions. Accurately annotating functions to proteins is crucial for understanding the intricate mechanisms of life and developing effective treatments for complex diseases. Traditional biological experiments struggle to keep pace with the growing number of known proteins. With the development of high-throughput sequencing technology, a wide variety of biological data provides the possibility to accurately predict protein functions by computational methods. Consequently, many computational methods have been proposed. Due to the diversity of application scenarios, it is necessary to conduct a comprehensive evaluation of these computational methods to determine the suitability of each algorithm for specific cases. In this study, we present a comprehensive benchmark, BeProf, to process data and evaluate representative computational methods. We first collect the latest datasets and analyze the data characteristics. Then, we investigate and summarize 17 state-of-the-art computational methods. Finally, we propose a novel comprehensive evaluation metric, design eight application scenarios and evaluate the performance of existing methods on these scenarios. Based on the evaluation, we provide practical recommendations for different scenarios, enabling users to select the most suitable method for their specific needs. All of these servers can be obtained from https://csuligroup.com/BEPROF and https://github.com/CSUBioGroup/BEPROF.

A review of enzyme design in catalytic stability by artificial intelligence.

The design of enzyme catalytic stability is of great significance in medicine and industry. However, traditional methods are time-consuming and costly. Hence, a growing number of complementary computational tools have been developed, e.g. ESMFold, AlphaFold2, Rosetta, RosettaFold, FireProt, ProteinMPNN. They are proposed for algorithm-driven and data-driven enzyme design through artificial intelligence (AI) algorithms including natural language processing, machine learning, deep learning, variational autoencoder/generative adversarial network, message passing neural network (MPNN). In addition, the challenges of design of enzyme catalytic stability include insufficient structured data, large sequence search space, inaccurate quantitative prediction, low efficiency in experimental validation and a cumbersome design process. The first principle of the enzyme catalytic stability design is to treat amino acids as the basic element. By designing the sequence of an enzyme, the flexibility and stability of the structure are adjusted, thus controlling the catalytic stability of the enzyme in a specific industrial environment or in an organism. Common indicators of design goals include the change in denaturation energy (ΔΔG), melting temperature (ΔTm), optimal temperature (Topt), optimal pH (pHopt), etc. In this review, we summarized and evaluated the enzyme design in catalytic stability by AI in terms of mechanism, strategy, data, labeling, coding, prediction, testing, unit, integration and prospect.

Interfacial Layers with Desolvation Function Induced Stable Deposition of Lithium Metal for Long-Cycling Lithium Metal Batteries.

The unstable solid electrolyte interface (SEI) formed by uncontrollable electrolyte degradation, which leads to dendrite growth and Coulombic efficiency decay, hinders the development of Li metal anodes. A controllable desolvation process is essential for the formation of stable SEI and improved lithium metal deposition behavior. Here, we show a functional artificial interface protective layer comprised of chondroitin sulfate-reduced graphene oxide (CrG), on which polar functional groups are distributed to effectively reduce the energy barrier for desolvation of Li+ and effectively alienate solvent molecules to avoid solvent involvement in SEI formation, thus promoting the formation of a LiF-rich SEI. Consequently, stable Coulombic efficiencies of 98.4% were achieved after 500 cycles in a Li//Cu cell. Moreover, the LiFePO4 full cells achieve steady circulation (470 cycles at 80%, 1 C) with a negative/positive electrode capacity ratio of 2.87. Our multifunctional artificial interface protective layer provides a new way to advance Li metal batteries.

A Unified Charge Storage Mechanism to Rationalize the Electrochemical Behavior of Quinone-Based Organic Electrodes in Aqueous Rechargeable Batteries.

Due to their eco-sustainability and versatility, organic electrodes are promising candidates for large-scale energy storage in rechargeable aqueous batteries. This is notably the case of aqueous hybrid batteries that pair the low voltage of a zinc anode with the high voltage of a quinone-based (or analogue of quinone-based) organic cathode. However, the mechanisms governing their charge-discharge cycles remain poorly understood and are even a matter of debate and controversy. No consensus exists on the charge carrier in mild aqueous electrolytes, especially when working in an electrolyte containing a multivalent metal cation such as Zn2+. In this study, we comprehensively investigate the electrochemical reactivity of two model quinones, chloranil, and duroquinone, either diluted in solution or incorporated into carbon-based composite electrodes. We demonstrate that a common nine-member square scheme proton-coupled electron transfer mechanism allows us to fully describe and rationalize their electrochemical behavior in relation to the pH and chemical composition of the aqueous electrolyte. Additionally, we highlight the crucial role played by the pKas associated with the reduced states of quinones in determining the nature of the charge carrier that compensates for the negative charges reversibly injected in the active material. Finally, contrary to the widely reported findings for Zn/organic batteries, we unequivocally establish that the predominant solid-state charge carriers in Zn2+-based mild aqueous electrolytes are not multivalent Zn2+ cations but rather protons supplied by the weakly acidic hexaaqua metal ions (i.e., [Zn(H2O)6]2+]).

Dominance of plasma-induced modulation in terahertz generation from gas filament.

In this paper, we revisit the fundamental mechanism responsible for terahertz generation from laser-induced plasma filament based on the photocurrent model by employing a blend of analytical calculation and numerical simulation. By using the frequency-decomposed finite-difference time-domain (FD-FDTD) method, the role of two-color field and photocurrent radiation in terahertz generation from plasma filament is visually separated, and the driving effect of photocurrent radiation is confirmed pretty significant within the process. Then, a pair of numerical experiments are taken to further analyze the driving effect of photocurrent radiation, and it is revealed that plasma-induced modulation to photocurrent radiation is actually the underlying physical mechanism of terahertz generation from plasma filament. Furthermore, a three-step diagram is introduced to reillustrate the overall physical process and provides a more comprehensive explanation. In addition, the mechanism of plasma-induced modulation to photocurrent radiation in terahertz generation is substantiated by taking theoretical prediction and numerical simulation of minimal filament length required for achieving stable backward terahertz emission, which directly confirms the validity and significance of plasma-induced modulation to photocurrent radiation in terahertz generation from laser-induced plasma filament.

Effect of gut flora mediated-bile acid metabolism on intestinal immune microenvironment.

According to reports, gut microbiota and metabolites regulate the intestinal immune microenvironment. In recent years, an increasing number of studies reported that bile acids (BAs) of intestinal flora origin affect T helper cells and regulatory T cells (Treg cells). Th17 cells play a pro-inflammatory role and Treg cells usually act in an immunosuppressive role. In this review, we emphatically summarised the influence and corresponding mechanism of different configurations of lithocholic acid (LCA) and deoxycholic acid (DCA) on intestinal Th17 cells, Treg cells and intestinal immune microenvironment. The regulation of BAs receptors G protein-coupled bile acid receptor 1 (GPBAR1/TGR5) and farnesoid X receptor (FXR) on immune cells and intestinal environment are elaborated. Furthermore, the potential clinical applications above were also concluded in three aspects. The above will help researchers better understand the effects of gut flora on the intestinal immune microenvironment via BAs and contribute to the development of new targeted drugs.

Extracellular vesicles remodel tumor environment for cancer immunotherapy.

Tumor immunotherapy has transformed neoplastic disease management, yet low response rates and immune complications persist as major challenges. Extracellular vesicles including exosomes have emerged as therapeutic agents actively involved in a diverse range of pathological conditions. Mounting evidence suggests that alterations in the quantity and composition of extracellular vesicles (EVs) contribute to the remodeling of the immune-suppressive tumor microenvironment (TME), thereby influencing the efficacy of immunotherapy. This revelation has sparked clinical interest in utilizing EVs for immune sensitization. In this perspective article, we present a comprehensive overview of the origins, generation, and interplay among various components of EVs within the TME. Furthermore, we discuss the pivotal role of EVs in reshaping the TME during tumorigenesis and their specific cargo, such as PD-1 and non-coding RNA, which influence the phenotypes of critical immune cells within the TME. Additionally, we summarize the applications of EVs in different anti-tumor therapies, the latest advancements in engineering EVs for cancer immunotherapy, and the challenges encountered in clinical translation. In light of these findings, we advocate for a broader understanding of the impact of EVs on the TME, as this will unveil overlooked therapeutic vulnerabilities and potentially enhance the efficacy of existing cancer immunotherapies.

Ultrasound-targeted microbubble destruction remodels tumour microenvironment to improve immunotherapeutic effect.

Cancer immunotherapy (CIT) has gained increasing attention and made promising progress in recent years, especially immune checkpoint inhibitors such as antibodies blocking programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4). However, its therapeutic efficacy is only 10-30% in solid tumours and treatment sensitivity needs to be improved. The complex tissue environment in which cancers originate is known as the tumour microenvironment (TME) and the complicated and dynamic TME is correlated with the efficacy of immunotherapy. Ultrasound-targeted microbubble destruction (UTMD) is an emerging technology that integrates diagnosis and therapy, which has garnered much traction due to non-invasive, targeted drug delivery and gene transfection characteristics. UTMD has also been studied to remodel TME and improve the efficacy of CIT. In this review, we analyse the effects of UTMD on various components of TME, including CD8+ T cells, tumour-infiltrating myeloid cells, regulatory T cells, natural killer cells and tumour vasculature. Moreover, UTMD enhances the permeability of the blood-brain barrier to facilitate drug delivery, thus improving CIT efficacy in vivo animal experiments. Based on this, we highlight the potential of immunotherapy against various cancer species and the clinical application prospects of UTMD.

Association of hepatitis B virus DNA levels with overall survival for advanced hepatitis B virus-related hepatocellular carcinoma under immune checkpoint inhibitor therapy.

BACKGROUND: High hepatitis B virus (HBV) DNA level is an independent risk factor for postoperative HBV-associated liver cancer recurrence. We sought to examine whether HBV DNA level and antiviral therapy are associated with survival outcomes in patients with advanced hepatocellular carcinoma (HCC) treated with anti-programmed cell death protein 1 (PD-1)based immunotherapy. METHODS: This single-institution retrospective analysis included 217 patients with advanced HBV-related HCC treated from 1 June 2018, through 30 December 2020. Baseline information was compared between patients with low and high HBV DNA levels. Overall survival (OS) and progression-free survival (PFS) were compared, and univariate and multivariate analyses were applied to identify potential risk factors for oncologic outcomes. RESULTS: The 217 patients included in the analysis had a median survival time of 20.6 months. Of these HBV-associated HCC patients, 165 had known baseline HBV DNA levels. Baseline HBV DNA level was not significantly associated with OS (P = 0.59) or PFS (P = 0.098). Compared to patients who did not receive antiviral therapy, patients who received antiviral therapy had significantly better OS (20.6 vs 11.1 months, P = 0.020), regardless of HBV DNA levels. Moreover, antiviral status (adjusted HR = 0.24, 95% CI 0.094-0.63, P = 0.004) was an independent protective factor for OS in a multivariate analysis of patients with HBV-related HCC. CONCLUSIONS: HBV viral load does not compromise the clinical outcome of patients with HBV-related HCC treated with anti-PD-1-based immunotherapy. The use of antiviral therapy significantly improves survival time of HBV-related HCC patients.

Broadband, compact and reflection-less silicon polarizer and polarization beam splitter using chirped anti-symmetric multimode nanobeams.

We present chirped anti-symmetric multimode nanobeams (CAMNs) based on silicon-on-insulator platforms, and describe their applications as broadband, compact, reflection-less, and fabrication-tolerant TM-pass polarizers and polarization beam splitters (PBSs). The anti-symmetric structural perturbations of a CAMN ensure that only contradirectional coupling between symmetric and anti-symmetric modes is possible, which can be exploited to block the unwanted back reflection of the device. The new possibility of introducing a large chirp on an ultra-short nanobeam-based device to overcome the operation bandwidth limitation due to the coupling coefficient saturation effect is also shown. The simulation results show that an ultra-compact CAMN with a length of ∼4.68 um can be used to develop a TM-pass polarizer or a PBS with an ultra-broad 20 dB extinction ratio (ER) bandwidth of >300 nm and an average insertion loss of <1.3 dB. The CAMN-based polarizer and PBS were fabricated and experimentally characterized in a wavelength range from 1507 to 1575 nm. The measured ERs were >20 dB over the entire tested wavelength range and the average insertion losses were <0.5 dB for both devices. The mean reflection suppression ratio of the polarizer was ∼26.4 dB. Large fabrication tolerances of ±60 nm in the waveguide widths of the devices were also demonstrated.

Mode thermo-optic coefficient engineering of sub-wavelength gratings and its application for a mode-insensitive switch.

It is shown that the thermo-optic (TO) coefficients of various waveguide modes of a sub-wavelength grating (SWG)-assisted strip waveguide is closely dependent on the various waveguide parameters with different dependencies, including the SWG width, strip waveguide width, duty cycle, and pitch. This offers what we believe to be new degrees of freedom in the design of TO coefficients for integrated-optic waveguides, opening the door to engineering the TO coefficients of individual spatial modes or polarization states using sub-wavelength structures. Such a capability is expected to offer new design possibilities for a variety of integrated photonic, thermo-optic devices. To demonstrate the application of the concept, a mode-insensitive switch on silicon-on-insulator using a TO coefficient-engineered SWG as a mode-independent, thermo-optic phase shifter is designed and experimentally demonstrated. The experimental results show that the switching powers of the TE0-TE2 modes are only ∼29 mW, and the maximum extinction ratios for the cross (bar) states are 38.2 dB (31 dB), 37.9 dB (37 dB), and 31.9 dB (20.5 dB) for the TE0-TE2 modes, respectively, at the wavelength of 1550 nm.

Inverse design of asymmetric Y-junctions for ultra-compact, broadband, and low crosstalk mode (de)multiplexers.

Asymmetric Y-junctions, compared with mode coupling-based devices, possess considerably smaller wavelength dependence and thus are more promising for ultra-broadband mode (de)multiplexing in integrated optics. However, these devices also feature relatively high mode crosstalk and insertion loss. Here, we show that the mode crosstalk and loss of an asymmetric Y-junction can be significantly reduced by optimizing the waveguide shape of the Y-junction using an adjoint-based inverse design. Based on such inverse-designed asymmetric Y-junctions, we realize ultra-compact, broadband, and low crosstalk silicon photonic TE00 & TE1 and TE0 & TE2 mode (de)multiplexers with sizes of only 4.5 × 1.2 µm2 and 6 × 1.4 µm2, respectively. From simulations it is shown that the TE0 & TE1 and TE0 & TE2 mode (de)multiplexers contain wide bandwidths of 160 nm (1460-1620 nm) and 140 nm (1460-1600 nm), respectively, over which the mode crosstalks are below about -20 dB, and the losses are <0.41 dB and <0.88 dB, respectively. The experimental results show that in the corresponding TE0 & TE1 and TE0 & TE2 mode division multiplexing systems, the crosstalks are less than -15.5 dB and -15 dB over the spectral ranges of 1453-1580 nm and 1460-1566 nm, respectively, and the losses are <1.7 dB at 1520 nm and <8.24 dB over the entire measured wavelength range.

Residual current under the combined effect of carrier envelope phase and chirp: phase shift and peak enhancement.

We theoretically investigate the residual current of linearly polarized light incident on graphene under the combined effect of carrier envelope phase and chirp. Phase shift and peak residual current enhancement are significantly obtained. Phase shift is the natural result of introducing a linear chirp in the presence of carrier envelope phase. By comparing the residual current integrated along the kx direction for different chirp rates and carrier envelope phases, the enhancement can be observed from two regions, where multiphoton interference is involved. By increasing the chirp rate, the light-graphene interaction turns from a non-perturbative to a perturbative regime. Thus the results of the combined effect can help to find suitable parameters to study regime transition and control of electronic dynamics. We expect that this study contributes to the signal processing at optical frequencies and to the development of optoelectronic integrated device applications.

Access to 3-Aminomethylated Maleimides via a Phosphine-Catalyzed Aza-Morita-Baylis-Hillman Type Coupling.

A designed method for the preparation of 3-aminomethylated maleimides via Morita-Baylis-Hillman (MBH) reaction was developed. This phosphine-catalyzed coupling adopted maleimides and 1,3,5-triazinanes as the substrate, giving a series of 3-aminomethylated maleimide derivatives with a double bond retained on the maleimide ring in 41-90% yield. Acylation, isomerization, and Michael addition of the obtained products demonstrated the synthetic application of the present protocol. The results of control experiments indicated that phosphorus ylide formation and elimination take place during the reaction pathway.

Detoxifying mycotoxins and antifungal properties of two rumen-derived Enterococcus species in artificially contaminated corn silages.

BACKGROUND: Mycotoxins contamination in food and feed has emerged as an issue of serious concern because they pose serious health risks to both humans and livestock. The study aimed to evaluate the effects of two rumen-derived Enterococcus spp. on fermentation and hygienic quality of artificially contaminated corn silages. The toxigenic fungal-infested (FI) and non-fungal infested (NFI) corn was harvested at 1/2 milk line stage and ensiled without additives (CON) or with Enterococcus faecalis (E) or Enterococcus faecium (M). RESULTS: The pH of FI silages was higher than that of NFI silages, the pH in NFI-M was lower than in NFI-CON. Inoculating E. faecium markedly increased lactic acid concentration compared to CON and E silages. Both E. faecium and E. faecalis decreased the deoxynivalenol (DON) and zearalenone (ZEN) concentrations compared with the CON for FI silages, while E. faecium was more effective in eliminating aflatoxin B1 (AFB1 ). The FI silage had higher bacterial and fungal Shannon indexes than NFI silages. The relative abundance (RA) of Aspergillus and Fusarium marked a decline from day 5 to day 90. Inoculating E. faecium and E. faecalis reduced the RA of Penicillium compared to CON. In vitro mycotoxins removal assay indicated that E. faecium was more effective in AFB1 detoxification while having lower detoxifying ZEN capacity than E. faecalis. CONCLUSION: Inoculating rumen-derived Enterococcus spp. isolates alleviated the negative effects of fungal infestation on the fermentation and hygienic quality of corn silages by changing the microbial communities and detoxifying mycotoxins. © 2023 Society of Chemical Industry.

Copper(I)-Catalyzed Direct Oxidative Annulation of 1,3-Dicarbonyl Compounds with Maleimides: Access to Polysubstituted Dihydrofuran Derivatives.

An efficient annulation method for the synthesis of polysubstituted dihydrofurans from 1,3-dicarbonyl compounds and maleimides is described. The reactions can afford furo[2,3-c]pyrrole derivatives with satisfactory yields. The developed strategy realizes the direct oxidative double C(sp3)-H functionalization in the presence of copper(I) salts and 2-(tert-butylperoxy)-2-methylpropane. Meanwhile, this protocol features a mild reaction condition and simple catalytic system. A reaction mechanism involving a single electron oxidation is also proposed.

Pharmacological Inhibition of Endogenous Hydrogen Sulfide Attenuates Breast Cancer Progression.

Hydrogen sulfide (H2S), a gaseous signaling molecule, is associated with the development of various malignancies via modulating various cellular signaling cascades. Published research has established the fact that inhibition of endogenous H2S production or exposure of H2S donors is an effective approach against cancer progression. However, the effect of pharmacological inhibition of endogenous H2S-producing enzymes (cystathionine-γ-lyase (CSE), cystathionine-ß-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MPST)) on the growth of breast cancer (BC) remains unknown. In the present study, DL-propargylglycine (PAG, inhibitor of CSE), aminooxyacetic acid (AOAA, inhibitor of CBS), and L-aspartic acid (L-Asp, inhibitor of 3-MPST) were used to determine the role of endogenous H2S in the growth of BC by in vitro and in vivo experiments. An in silico study was also performed to confirm the results. Corresponding to each enzyme in separate groups, we treated BC cells (MCF-7 and MDA-MB-231) with 10 mM of PAG, AOAA, and L-Asp for 24 h. Findings reveal that the combined dose (PAG + AOAA + L-Asp) group showed exclusive inhibitory effects on BC cells' viability, proliferation, migration, and invasion compared to the control group. Further, treated cells exhibited increased apoptosis and a reduced level of phospho (p)-extracellular signal-regulated protein kinases such as p-AKT, p-PI3K, and p-mTOR. Moreover, the combined group exhibited potent inhibitory effects on the growth of BC xenograft tumors in nude mice, without obvious toxicity. The molecular docking results were consistent with the wet lab experiments and enhanced the reliability of the drugs. In conclusion, our results demonstrate that the inhibition of endogenous H2S production can significantly inhibit the growth of human breast cancer cells via the AKT/PI3K/mTOR pathway and suggest that endogenous H2S may act as a promising therapeutic target in human BC cells. Our study also empowers the rationale to design novel H2S-based anti-tumor drugs to cure BC.

ZnO Composite Graphene Coating Micro-Fiber Interferometer for Ultraviolet Detection.

A simple and reliable ultraviolet sensing method with high sensitivity is proposed. ZnO and ZnO composite graphene are successfully prepared by the hydrothermal method. The optical fiber sensor is fabricated by coating the single-mode-taper multimode-single-mode (STMS) with different shapes of ZnO. The effects of the sensitivity of ultraviolet sensors are further investigated. The results show that the sensor with ZnO nanosheets exhibits a higher sensitivity of 357.85 pm/nW·cm-2 for ultraviolet sensing ranging from 0 to 4 nW/cm2. The ultraviolet characteristic of STMS coated flake ZnO composite graphene has been demonstrated with a sensitivity of 427.76 pm/nW·cm-2. The combination of sensitive materials and optical fiber sensing technology provides a novel and convenient platform for ultraviolet detection technology.

Iodine-Catalyzed Regioselective Oxidative Cyclization of Aldehyde Hydrazones with Electron-Deficient Olefins for the Synthesis of Mefenpyr-Diethyl.

A regioselective synthesis of polysubstituted dihydropyrazoles and pyrazoles through an iodine-catalyzed oxidative cyclization strategy of aldehyde hydrazones with electron-deficient olefins is described. The protocol adopts very mild reaction conditions and provides desirable yields. The reaction is supposed to proceed via a cascade C-H functionalization, C-N bond formation, and oxidation sequential processes. The overall simplicity and regioselectivity of the catalytic system make this approach a valuable and step-economical tool to construct a C-C bond for the synthesis of Mefenpyr-Diethyl.

Wall-Normal Variation of Spanwise Streak Spacing in Turbulent Boundary Layer With Low-to-Moderate Reynolds Number.

Low-speed streaks in wall-bounded turbulence are the dominant structures in the near-wall turbulent self-sustaining cycle. Existing studies have well characterized their spanwise spacing in the buffer layer and below. Recent studies suggested the existence of these small-scale structures in the higher layer where large-scale structures usually receive more attention. The present study is thus devoted to extending the understanding of the streak spacing to the log layer. An analysis is taken on two-dimensional (2D) wall-parallel velocity fields in a smooth-wall turbulent boundary layer with R e τ = 440∼2400, obtained via either 2D Particle Image Velocimetry (PIV) measurement taken here or public Direct Numerical Simulation (DNS). Morphological-based streak identification analysis yields a R e -independent log-normal distribution of the streak spacing till the upper bound of the log layer, based on which an empirical model is proposed to account for its wall-normal growth. The small-scale part of the spanwise spectra of the streamwise fluctuating velocity below y + = 100 is reasonably restored by a synthetic simulation that distributes elementary streak units based on the proposed empirical streak spacing model, which highlights the physical significance of streaks in shaping the small-scale part of the velocity spectra beyond the buffer layer.