Chemical signaling in biofilm-mediated biofouling.

Biofouling is the undesirable accumulation of living organisms and their metabolites on submerged surfaces. Biofouling begins with adhesion of biomacromolecules and/or microorganisms and can lead to the subsequent formation of biofilms that are predominantly regulated by chemical signals, such as cyclic dinucleotides and quorum-sensing molecules. Biofilms typically release chemical cues that recruit or repel other invertebrate larvae and algal spores. As such, harnessing the biochemical mechanisms involved is a promising avenue for controlling biofouling. Here, we discuss how chemical signaling affects biofilm formation and dispersion in model species. We also examine how this translates to marine biofouling. Both inductive and inhibitory effects of chemical cues from biofilms on macrofouling are also discussed. Finally, we outline promising mitigation strategies by targeting chemical signaling to foster biofilm dispersion or inhibit biofouling.

UBC18 E2 conjugating enzyme depends on SINAT1 E3 ligase to destabilize the ESCRT component FREE1 in plant iron deficiency responses.

E2 ubiquitin-conjugating enzymes play a crucial role in the ubiquitination process by catalyzing ubiquitin transfer. Although the function of ubiquitin-protein ligases (E3s) in plants response to diverse abiotic stress by targeting specific substrates has been well studied, the involvement of E2s in environmental responses and their downstream targets are not well understood. In this study, we demonstrated that the E2 ubiquitin-conjugating enzyme 18 (UBC18) influences the stability of FREE1 to modulate iron deficiency stress. UBC18 affects the ubiquitination of FREE1 and promotes its degradation, and overexpression of UBC18 decreases plants' sensitivity to iron deficiency by reducing FREE1 level, whereas the ubc18 mutant exhibits sensitivity due to elevated FREE1 accumulation. This study also identified that lysine residues K227, K295, K315, and K540 are required for FREE1 ubiquitination and stability regulation. Mutating these lysine residues in FREE1 resulted in plants' sensitivity to iron starvation. Taken together, our findings shed light on the mechanism of UBC18 in responding to iron deficiency stress by modulating the abundance of FREE1, and further elucidate the role of ubiquitination sites in FREE1 stability regulation and the plant iron deficiency response.

miR-148b-5p regulates hypercalciuria and calcium-containing nephrolithiasis.

Calcium-containing stones represent the most common form of kidney calculi, frequently linked to idiopathic hypercalciuria, though their precise pathogenesis remains elusive. This research aimed to elucidate the molecular mechanisms involved by employing urinary exosomal microRNAs as proxies for renal tissue analysis. Elevated miR-148b-5p levels were observed in exosomes derived from patients with kidney stones. Systemic administration of miR-148b-5p in rat models resulted in heightened urinary calcium excretion, whereas its inhibition reduced stone formation. RNA immunoprecipitation combined with deep sequencing identified miR-148b-5p as a suppressor of calcitonin receptor (Calcr) expression, thereby promoting urinary calcium excretion and stone formation. Mice deficient in Calcr in distal epithelial cells demonstrated elevated urinary calcium excretion and renal calcification. Mechanistically, miR-148b-5p regulated Calcr through the circRNA-83536/miR-24-3p signaling pathway. Human kidney tissue samples corroborated these results. In summary, miR-148b-5p regulates the formation of calcium-containing kidney stones via the circRNA-83536/miR-24-3p/Calcr axis, presenting a potential target for novel therapeutic interventions to prevent calcium nephrolithiasis.

TexSe1-x Shortwave Infrared Photodiode Arrays with Monolithic Integration.

TexSe1-x shortwave infrared (SWIR) photodetectors show promise for monolithic integration with readout integrated circuits (ROIC), making it a potential alternative to conventional expensive SWIR photodetectors. However, challenges such as a high dark current density and insufficient detection performance hinder their application in large-scale monolithic integration. Herein, we develop a ZnO/TexSe1-x heterojunction photodiode and synergistically address the interfacial elemental diffusion and dangling bonds via inserting a well-selected 0.3 nm amorphous TeO2 interfacial layer. The optimized device achieves a reduced dark current density of -3.5 × 10-5 A cm-2 at -10 mV, a broad response from 300 to 1700 nm, a room-temperature detectivity exceeding 2.03 × 1011 Jones, and a 3 dB bandwidth of 173 kHz. Furthermore, for the first time, we monolithically integrate the TexSe1-x photodiodes on ROIC (64 × 64 pixels) with the largest-scale array among all TexSe1-x-based detectors. Finally, we demonstrate its applications in transmission imaging and substance identification.

MXene-Based Pressure Sensor with a Self-Healing Property for Joule Heating and Friction Sliding.

As a kind of flexible electronic device, flexible pressure sensor has attracted wide attention in medical monitoring and human-machine interaction. With the continuous deepening of research, high-sensitivity sensor is developing from single function to multi-function. However, Current multifunctional sensors lack the ability to integrate joule heating, detect sliding friction, and self-healing. Herein, a MXene/polyurethane (PU) flexible pressure sensor with a self-healing property for joule heating and friction sliding is fabricated. The MXene/PU sensitive layer with special spinosum structure is prepared by a simple spraying method. After face-to-face assembly of the sensitive layers, the MXene/PU flexible pressure sensor is obtained and showed excellent sensitivity (150.65 kPa-1), fast response/recovery speed (75.5/63.9 ms), and good stability (10 000 cycles). Based on the self-healing property of PU, the sensor also has the ability to heal after mechanical damage. In addition, the sensor realizes the joule heating function under low voltage, and has the real-time monitoring ability of sliding objects. Combined with low cost and simple manufacturing method, the multi-functional MXene/PU flexible sensor shows a wide range of application potential in human activity monitoring, thermal management, and slip recognition.

Natural Polyphenol Delivered Methylprednisolone Achieve Targeted Enrichment for Acute Spinal Cord Injury Therapy.

The strong anti-inflammatory effect of methylprednisolone (MP) is a necessary treatment for various severe cases including acute spinal cord injury (SCI). However, concerns have been raised regarding adverse effects from MP, which also severely limits its clinical application. Natural polyphenols, due to their rich phenolic hydroxyl chemical properties, can form dynamic structures without additional modification, achieving targeted enrichment and drug release at the disease lesion, making them a highly promising carrier. Considering the clinical application challenges of MP, a natural polyphenolic platform is employed for targeted and efficient delivery of MP, reducing its systemic side effects. Both in vitro and SCI models demonstrated polyphenols have multiple advantages as carriers for delivering MP: (1) Achieved maximum enrichment at the injured site in 2 h post-administration, which met the desires of early treatment for diseases; (2) Traceless release of MP; (3) Reducing its side effects; (4) Endowed treatment system with new antioxidative properties, which is also an aspect that needs to be addressed for diseases treatment. This study highlighted a promising prospect of the robust delivery system based on natural polyphenols can successfully overcome the barrier of MP treatment, providing the possibility for its widespread clinical application.

Plasma exosomes from patients with active thyroid-associated orbitopathy induce inflammation and fibrosis in orbital fibroblasts.

BACKGROUND: The pathogenesis of thyroid-associated orbitopathy (TAO) remains incompletely understand. The interaction between immunocytes and orbital fibroblasts (OFs) play a critical role in orbital inflammatory and fibrosis. Accumulating reports indicate that a significant portion of plasma exosomes (Pla-Exos) are derived from immune cells; however, their impact upon OFs function is unclear. METHODS: OFs were primary cultured from inactive TAO patients. Exosomes isolated from plasma samples of patients with active TAO and healthy controls (HCs) were utilized for functional and RNA cargo analysis. Functional analysis in thymocyte differentiation antigen-1+ (Thy-1+) OFs measured expression of inflammatory and fibrotic markers (mRNAs and proteins) and cell activity in response to Pla-Exos. RNA cargo analysis was performed by RNA sequencing and RT-qPCR. Thy-1+ OFs were transfected with miR-144-3p mimics/inhibitors to evaluate its regulation of inflammation, fibrosis, and proliferation. RESULTS: Pla-Exos derived from active TAO patients (Pla-ExosTAO-A) induced stronger production of inflammatory cytokines and hyaluronic acid (HA) in Thy-1+ OFs while inhibiting their proliferation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and single sample gene set enrichment analysis (ssGSEA) suggested that the difference in mRNA expression levels between Pla-ExosTAO-A and Pla-ExosHC was closely related to immune cells. Differential expression analysis revealed that 62 upregulated and 45 downregulated miRNAs in Pla-ExosTAO-A, with the elevation of miR-144-3p in both Pla-Exos and PBMCs in active TAO group. KEGG analysis revealed that the target genes of differentially expressed miRNA and miR-144-3p enriched in immune-related signaling pathways. Overexpression of the miR-144-3p mimic significantly upregulated the secretion of inflammatory cytokines and HA in Thy-1+ OFs while inhibiting their proliferation. CONCLUSION: Pla-Exos derived from patients with active TAO were immune-active, which may be a long-term stimulus casual for inflammatory and fibrotic progression of TAO. Our finding suggests that Pla-Exos could be used as biomarkers or treatment targets in TAO patients.

ROK family regulator NagC promotes prodigiosin biosynthesis independent of N-acetylglucosamine in Serratia sp. ATCC 39006.

Serratia sp. ATCC 39006 is an important model strain for the study of prodigiosin production, whose prodigiosin biosynthesis genes (pigA-O) are arranged in an operon. Several transcription factors have been shown to control the transcription of the pig operon. However, since the regulation of prodigiosin biosynthesis is complex, the regulatory mechanism for this process has not been well established. In most γ-proteobacteria, the ROK family regulator NagC acts as a global transcription factor in response to N-acetylglucosamine (GlcNAc). In Serratia sp. ATCC 39006, NagC represses the transcription of two divergent operons, nagE and nagBAC, which encode proteins involved in the transport and metabolism of GlcNAc. Moreover, NagC directly binds to a 21-nt region that partially overlaps the -10 and -35 regions of the pig promoter and promotes the transcription of prodigiosin biosynthesis genes, thereby increasing prodigiosin production. Although NagC still acts as both repressor and activator in Serratia sp. ATCC 39006, its transcriptional regulatory activity is independent of GlcNAc. NagC was first found to regulate antibiotic biosynthesis in Gram-negative bacteria, and NagC-mediated regulation is not responsive to GlcNAc, which contributes to future studies on the regulation of secondary metabolism by NagC in other bacteria. IMPORTANCE: The ROK family transcription factor NagC is an important global regulator in the γ-proteobacteria. A large number of genes involved in the transport and metabolism of sugars, as well as those associated with biofilm formation and pathogenicity, are regulated by NagC. In all of these regulations, the transcriptional regulatory activity of NagC responds to the supply of GlcNAc in the environment. Here, we found for the first time that NagC can regulate antibiotic biosynthesis, whose transcriptional regulatory activity is independent of GlcNAc. This suggests that NagC may respond to more signals and regulate more physiological processes in Gram-negative bacteria.

Functional studies on tandem carbohydrate-binding modules of a multimodular enzyme possessing two catalytic domains.

Although functional studies on carbohydrate-binding module (CBM) have been carried out extensively, the role of tandem CBMs in the enzyme containing multiple catalytic domains (CDs) is unclear. Here, we identified a multidomain enzyme (Lc25986) with a novel modular structure from lignocellulolytic bacterial consortium. It consists of a mannanase domain, two CBM65 domains (LcCBM65-1/LcCBM65-2), and an esterase domain. To investigate CBM function and domain interactions, full-length Lc25986 and its variants were constructed and used for enzymatic activity, binding, and bioinformatic analyses. The results showed that LcCBM65-1 and LcCBM65-2 both bind mannan and xyloglucan but not cellulose or ß-1,3-1,4-glucan, which differs from the ligand specificity of reported CBM65s. Compared to LcCBM65-2, LcCBM65-1 showed a stronger ligand affinity and a preference for acetylation sites. Both CBM65s stimulated the enzymatic activities of their respective neighboring CDs against acetylated mannan, but did not contribute to the activities of the distal CDs. The time course of mannan hydrolysis indicated that the full-length Lc25986 was more effective in the complete degradation of mixed acetyl/non-acetyl substrates than the mixture of single-CD mutants. When acting on complex substrates, LcCBM65-1 not only improved the enzymatic activity of the mannanase domain, but also directed the esterase domain to the acetylated polysaccharides. LcCBM65-2 adopted a low affinity to reduce interference with the catalysis of the mannanase domain. These results demonstrate the importance of CBMs for the synergism between the two CDs of a multidomain enzyme and suggest that they contribute to the adequate degradation of complex substrates such as plant cell walls. IMPORTANCE: Lignocellulolytic enzymes, particularly those of bacterial origin, often harbor multiple carbohydrate-binding modules (CBMs). However, the function of CBM multivalency remains poorly understood. This is especially true for enzymes that contain more than one catalytic domain (CD), as the interactions between CDs, CBMs, and CDs and CBMs can be complex. Our research demonstrates that homogeneous CBMs can have distinct functions in a multimodular enzyme. The tandem CBMs coordinate the CDs in catalytic conflict through their differences in binding affinity, ligand preference, and arrangement within the full-length enzyme. Additionally, although the synergism between mannanase and esterase is widely acknowledged, our study highlights the benefits of integrating the two enzymes into a single entity for the degradation of complex substrates. In summary, these findings enhance our understanding of the intra-synergism of a multimodular enzyme and emphasize the significance of multiple CBMs in this context.

CXCL6 promotes the progression of NAFLD through regulation of PPARα.

An increasing number of studies have shown that Nonalcoholic fatty liver disease (NAFLD) is strongly associated with obesity, insulin resistance, dyslipidemia, hypertension and metabolic syndrome, but its specific pathogenesis remains unclear. By analyzing GEO database, we found CXCL6 was upregulated in liver tissues of patients with NAFLD. We also confirmed with qPCR that CXCL6 is highly expressed in serum of patients with NAFLD. To identify the underlying impact of CXCL6 on NAFLD, we established animal and cell models of NAFLD. Similarly, we confirmed by qPCR and Western blot that CXCL6 was upregulated in the NAFLD model in vitro and vivo. After transfecting NAFLD cells with siRNA targeting CXCL6 (si-CXCL6), a series of functional experiments were carried out, and these data indicated that the inhibition of CXCL6 reduced intracellular lipid deposition, decreased AST, ALT and TG level, facilitate cell proliferation and suppress their apoptosis. Furthermore, western blot and qPCR analyses displayed that the suppression of CXCL6 could raise the PPARα expression, but PPAR α inhibitor, GW6471 could partially counteract this effect. What's more, Oil Red O staining, biochemical analyzer and TG detection kit revealed that GW6471 could reverse the inhibitory effect of si-CXCL6 on NAFLD. In summary, we provide convincing evidence that CXCL6 is markedly elevated in NAFLD, and the CXCL6/PPARα regulatory network mediates disease progression of NAFLD.

Observation of multiple topological bound states in the continuum in the photonic bilayer trimer lattice.

A topological bound state in the continuum (TBIC) is a novel topological phase that has attracted significant attention. Different from conventional topological insulators (TIs), where boundary states reside within gaps, TBICs can support unconventional boundary states that remain isolated from the surrounding bulk states. In this work, we experimentally demonstrate multiple TBICs in photonic bilayer trimer lattices using femtosecond laser writing technology. By modulating the interlayer coupling between two trimer chains, we observe the emergence of two distinct types of TBICs. Moreover, we experimentally achieve the coexistence of in-gap topological states and TBICs and demonstrate the transformation between them. Our work unveils new insights into the flexible construction of TBICs, and this method can be easily applied to other one-dimensional topological structures, offering promising avenues for further research.

Low-threshold AlGaN-based deep ultraviolet laser enabled by a nanoporous cladding layer.

We demonstrated an AlGaN-based multiple-quantum-well (MQW) deep ultraviolet (DUV) laser at 278 nm using a nanoporous (NP) n-AlGaN as the bottom cladding layer grown on the sapphire substrate. The laser has a very-low-threshold optically pumped power density of 79 kW/cm2 at room temperature and a transverse electric (TE)-polarization-dominant emission. The high optical confinement factor of 9.12% benefiting from the low refractive index of the nanoporous n-AlGaN is the key to enable a low-threshold lasing. The I-V electrical measurement demonstrates that an ohmic contact can be still achieved in the NP n-AlGaN with a larger but acceptable resistance, which indicates it is compatible with electrically driven laser devices. Our work provides insights into the design and fabrication of low-threshold lasers emitting in the DUV regime.

Experimental investigation on backscattering interference cancellation for full-duplex UOWC based on time-reversal preprocessing.

A co-frequency and full-duplex (FD) underwater optical wireless communication (UOWC) system has the potential to significantly enhance spectral efficiency, reduce complexity, and further facilitate UOWC networking. However, the inevitable performance degradation due to self-interference introduced by backscattering presents a significant challenge. In this paper, we first experimentally explore the inherent characteristics of the underwater backscattering channel. Subsequently, we propose a digital-domain backscattering interference cancellation (BIC) algorithm for FD-UOWC systems, incorporating a time-reversal preprocessing. We then experimentally investigate the communication performance of an FD-UOWC system to verify the feasibility of the proposed BIC algorithm under different channel conditions. The experimental results validate the effectiveness of the proposed method, yielding substantial enhancements in bit error rate performance across diverse scenarios.

Experimental saturation characteristics of the PMT and adaptive compensation algorithm for OWC.

Orthogonal frequency division multiplexing (OFDM) utilizes numerous sub-carriers to achieve high transmission data rates. The frequency selectivity of the channel becomes a crucial factor influencing the communication performance of OFDM-based systems. In optical wireless communication (OWC) systems, the photomultiplier tube (PMT) may experience saturation when the incident optical power approaches its saturation threshold. This paper, for the first time, characterizes the saturation levels of a high-speed PMT based on the measured amplitude in the time domain and the output response of the PMT in the frequency domain. Additionally, an adaptive optical saturation compensation algorithm, leveraging an electronically controlled variable optical attenuator, is proposed to realize a reliable OWC system. Experimental results demonstrate that the proposed saturation compensation method achieves a higher tolerance to large dynamic signal and background radiation compared with that without compensation, while maintaining a satisfactory bit error rate.

On-DNA Morita-Baylis-Hillman Reaction: Accessing Targeted Covalent Inhibitor Motifs in DNA-Encoded Libraries.

We herein present the first application of the on-DNA Morita-Baylis-Hillman (MBH) reaction for the creation of pharmaceutically relevant targeted covalent inhibitors (TCIs) with an α-hydroxyl Michael acceptor motif. Adapting a DNA-compatible organocatalytic process, this MBH reaction for covalent selection-capable DNA encoded library (DEL) synthesis grants access to densely functionalized and versatile precursors to explore novel chemical space for molecule recognition in drug discovery. Most importantly, this methodology sheds light on potentially unexpected reaction outcomes of the MBH reaction.

Wide dynamic range signal detection for underwater optical wireless communication using a PMT detector.

In the underwater optical wireless communication (UOWC) scenario, a photomultiplier tube (PMT) with higher sensitivity, lower noise, and a larger receiver area is employed as the photon detector to further extend the transmission distance. Due to the complex underwater environment, the high directionality of the light beam, and the vibration of a transceiver, the incident optical power usually spans a very wide dynamic range, and the PMT may operate in any one of the three regimes: pulse, transition, and waveform. While it is difficult to obtain the analytical characterization of the output electric signals across these regimes, this paper resorts to experimental measurements of the upsampled discrete samples within a training symbol duration. Among different statistical distribution fitting options, generalized extreme value (GEV) distribution is found to show excellent performance in fitting the probability density function (PDF) of either multiple samples or the superimposition of all samples within a symbol duration. Then joint sample distribution (JSD) based and superimposed sample distribution (SSD) based symbol detection methods are proposed by adopting the GEV distribution and log-likelihood ratio (LLR) testing criterion. The proposed methods are experimentally evaluated under different received signal optical powers, data rates, and sampling rates. They are shown to outperform the Poisson and Gaussian based maximum likelihood detection methods which are employed for the pulse regime and waveform regime respectively. Furthermore, the effectiveness of the proposed methods in alleviating strong ambient radiation is experimentally verified.

Multilevel polarization shift keying modulation for turbulence-robust underwater optical wireless communication.

Turbulence is an intractable issue for underwater optical wireless communication (UOWC). Most literature has been mainly focused on the modeling of turbulence channels and performance analysis rather than mitigation of the turbulence effect, especially from the experimental aspects. In this paper, a multilevel polarization shift keying (PolSK) modulation based UOWC system is established utilizing a 15 m-long water tank, and the system performance is investigated under specific temperature gradient-induced turbulence and various transmitted optical powers. Experimental results show the feasibility of the PolSK in alleviating the effect of turbulence, and the bit error rate performance significantly outperforms traditional intensity-based modulation schemes which have difficulty in obtaining an optimal decision threshold in a turbulence channel.

Photonic topological subspace-induced bound states in the continuum.

Bound states in the continuum (BICs) are intriguing localized states that possess eigenvalues embedded within the continuum of extended states. Recently, a combination of topological band theory and BIC physics has given rise to a novel form of topological matter known as topological BICs. In this work, we experimentally demonstrate the photonic topological subspace-induced BICs. By using femtosecond-laser writing, we experimentally establish a photonic nontrivial three-leg ladder lattice, thereby directly observe the localized propagation of two kinds of topological edge states which exist at different boundaries. Interestingly, such edge states appear in the continuum of the bulk modes, and the topological properties are inherited from its independent subspace Hamiltonian which contains a celebrated Su-Schrieffer-Heeger lattice. This work not only presents a novel, to the best of our knowledge, platform for investigating topological physics in optics, but also unveils exciting prospects for future exploration of other remarkable BICs.

Topological edge states in photonic decorated trimer lattices.

In recent years, topological insulators have been extensively studied in one-dimensional periodic systems, such as Su-Schrieffer-Heeger and trimer lattices. The remarkable feature of these one-dimensional models is that they support topological edge states, which are protected by lattice symmetry. To further study the role of lattice symmetry in one-dimensional topological insulators, here we design a modified version of the conventional trimer lattices, i.e., decorated trimer lattices. Using the femtosecond laser writing technique, we experimentally establish a series of one-dimensional photonic decorated trimer lattices with and without inversion symmetry, thereby directly observing three kinds of topological edge state. Interestingly, we demonstrate that the additional vertical intracell coupling strength in our model can change the energy band spectrum, thereby generating unconventional topological edge states with a longer localization length in another boundary. This work offers novel insight into topological insulators in one-dimensional photonic lattices.

Observation of higher-order topological corner states in photonic two-dimensional trimer lattices.

We demonstrate the first, to the best of our knowledge, experimental observation of higher-order topological corner states in the photonic two-dimensional (2D) trimer lattices. Using a femtosecond laser direct writing technology, we experimentally fabricate a series of 2D trimer lattices with different open boundary conditions and thereby observe two kinds of 0D topological corner states, i.e., topological corner states and topological defect corner states. Interestingly, these corner states and defect corner states can not only exist in the bandgap but also coexist with the bulk states and show obvious localization properties. This work provides fresh perspectives on higher-order topology in artificial microstructures.