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Abstract The rapid rise of antibiotic resistance and slow discovery of new antibiotics have threatened global health. While novel phage lysins have emerged as potential antibacterial agents, experimental screening methods for novel lysins pose significant challenges due to the enormous workload. Here, the first unified software package, namely DeepLysin, is developed to employ artificial intelligence for mining the vast genome reservoirs (“dark matter”) for novel antibacterial phage lysins. Putative lysins are computationally screened from uncharacterized Staphylococcus aureus phages and 17 novel lysins are randomly selected for experimental validation. Seven candidates exhibit excellent in vitro antibacterial activity, with LLysSA9 exceeding that of the best‐in‐class alternative. The efficacy of LLysSA9 is further demonstrated in mouse bloodstream and wound infection models. Therefore, this study demonstrates the potential of integrating computational and experimental approaches to expedite the discovery of new antibacterial proteins for combating increasing antimicrobial resistance.

The notion that obesity can be a protective factor for bone health is a topic of ongoing debate. Increased body weight may have a positive impact on bone health due to its mechanical effects and the production of estrogen by adipose tissue. However, recent studies have found a higher risk of bone fracture and delayed bone healing in elderly obese patients, which may be attributed to the heightened risk of bone immune regulation disruption associated with obesity. The balanced functions of bone cells such as osteoclasts, osteoblasts, and osteocytes, would be subverted by aberrant and prolonged immune responses under obese conditions. This review aims to explore the intricate relationship between obesity and bone health from the perspective of osteoimmunology, elucidate the impact of disturbances in bone immune regulation on the functioning of bone cells, including osteoclasts, osteoblasts, and osteocytes, highlighting the deleterious effects of obesity on various diseases development such as rheumatoid arthritis (RA), osteoarthritis (AS), bone fracture, periodontitis. On the one hand, weight loss may achieve significant therapeutic effects on the aforementioned diseases. On the other hand, for patients who have difficulty in losing weight, the osteoimmunological therapies could potentially serve as a viable approach in halting the progression of these disease. Additional research in the field of osteoimmunology is necessary to ascertain the optimal equilibrium between body weight and bone health.

Abstract Cluster of differentiation 31 (CD31), phalloidin and alpha smooth muscle actin (α-SMA) have been widely applied to label the cerebral blood vessels in the past years. Although CD31 is mainly used as endothelial marker in determining the cerebral capillaries, it seems likely that its labeling efficiency is closely correlated with the antibodies from the polyclonal or monoclonal one, as well as the conditions of blood vessels. In order to test this phenomenon, we compared the labeling characteristics of goat polyclonal anti-CD31 (gP-CD31) and mouse monoclonal anti-CD31 (mM-CD31) with those of phalloidin and α-SMA on the rat brain in health and ischemia/reperfusion (I/R) with the middle cerebral artery occlusion. By multiple immunofluorescence staining, it was found that gP-CD31 labeling expressed extensively on the cerebral capillaries forming the vascular networks on the normal and ischemic regions, but mM-CD31 labeling mainly presented on the capillaries in the ischemic region. In contrast to the vascular labeling with gP-CD31, phalloidin and α-SMA were mainly expressed on the wall of cortical penetrating arteries, and less on that of capillaries. By three-dimensional reconstruction analysis, it was clearly shown that gP-CD31 labeling was mainly located on the lumen side of vascular wall and was surrounded by phalloidin labeling and α-SMA labeling. These results indicate that gP-CD31 is more sensitive than mM-CD31 for labeling the cerebral vasculature, and is highly compatible with phalloidin and α-SMA for evaluating the cerebral vascular networks under the physiological and pathological conditions.

P1 protein, the most divergent protein of virus members in the genus Potyvirus of the family Potyviridae, is required for robust infection and host adaptation. However, how P1 affects viral proliferation is still largely elusive. In this work, a total number of eight potential P1-interacting Arabidopsis proteins were identified by the yeast-two-hybrid screening using the turnip mosaic virus (TuMV)-encoded P1 protein as the bait. Among which, the stress upregulated NODULIN 19 (NOD19) was selected for further characterization. The bimolecular fluorescent complementation assay confirmed the interaction between TuMV P1 and NOD19. Expression profile, structure, and subcellular localization analyses showed that NOD19 is a membrane-associated protein expressed mainly in plant aerial parts. Viral infectivity assay showed that the infection of turnip mosaic virus and soybean mosaic virus was attenuated in the null mutant of Arabidopsis NOD19 and NOD19-knockdown soybean seedlings, respectively. Together, these data indicate that NOD19 is a P1-interacting host factor required for robust infection.

IntroductionNumerous studies have shown that aging has important effects on specific functional networks of the brain and leads to brain functional connectivity decline. However, no studies have addressed the effect of aging at the whole-brain level by studying both brain functional networks (i.e., within-network connectivity) and their interaction (i.e., between-network connectivity) as well as their joint changes.MethodsIn this work, based on a large sample size of neuroimaging data including 6300 healthy adults aged between 49 and 73 years from the UK Biobank project, we first use our previously proposed priori-driven independent component analysis (ICA) method, called NeuroMark, to extract the whole-brain functional networks (FNs) and the functional network connectivity (FNC) matrix. Next, we perform a two-level statistical analysis method to identify robust aging-related changes in FNs and FNCs, respectively. Finally, we propose a combined approach to explore the synergistic and paradoxical changes between FNs and FNCs.ResultsResults showed that the enhanced FNCs mainly occur between different functional domains, involving the default mode and cognitive control networks, while the reduced FNCs come from not only between different domains but also within the same domain, primarily relating to the visual network, cognitive control network, and cerebellum. Aging also greatly affects the connectivity within FNs, and the increased within-network connectivity along with aging are mainly within the sensorimotor network, while the decreased within-network connectivity significantly involves the default mode network. More importantly, many significant joint changes between FNs and FNCs involve default mode and sub-cortical networks. Furthermore, most synergistic changes are present between the FNCs with reduced amplitude and their linked FNs, and most paradoxical changes are present in the FNCs with enhanced amplitude and their linked FNs.DiscussionIn summary, our study emphasizes the diversity of brain aging and provides new evidence via novel exploratory perspectives for non-pathological aging of the whole brain.

Enshi Yulu, a renowned Chinese steamed green tea, is highly valued for its unique sensory attributes. To enhance our comprehensive understanding of the metabolic variation induced by steaming fixation, we investigated the overall chemical profiles and organoleptic quality of Enshi Yulu from different tea cultivars (Longjing 43, Xiapu Chunbolv, and Zhongcha 108). The relationships between sensory traits and non-volatiles/volatiles were evaluated. A total of 58 volatiles and 18 non-volatiles were identified as characteristic compounds for discriminating among the three tea cultivars, and the majority were correlated with sensory attributes. The “mellow” taste was associated with L-aspartic acid, L-asparagine, L-tyrosine, L-valine, EGC, EC, and ECG, while gallic acid and theobromine contributed to the “astringent” taste. “Kokumi” contributors were identified as L-methionine, L-lysine, and GCG. Enshi Yulu displayed a “pure” and “clean and refreshing” aroma associated with similar volatiles like benzyl alcohol, δ-cadinene, and muurolol. The composition of volatile compounds related to the “chestnut” flavor was complex, including aromatic heterocycles, acids, ketones, terpenes, and terpene derivatives. The key contributors to the “fresh” flavor were identified as linalool oxides. This study provides valuable insights into the sensory-related chemical profiles of Enshi Yulu, offering essential information for flavor and quality identification of Enshi Yulu.

In this article, we consider the following nonlocal fractional Kirchhoff-type elliptic systems $ \begin{equation*} \left\{\begin{array}{l} -M_{1}\left(\int_{\mathbb{R}^{N}\times\mathbb{R}^{N}}\frac{|\eta(x)-\eta(y)|^{^{p(x, y)}}}{p(x, y)|x-y|^{N+p(x, y)s(x, y)}} \ \ \ \ \ dxdy +\int_{\Omega}\frac{|\eta|^{\overline{p}(x)}}{\overline{p}(x)}dx\right) \left(\Delta_{p(\cdot)}^{s(\cdot)}\eta-|\eta|^{\overline{p}(x)}\eta\right)\\ \; \; \; = \lambda F_{\eta}(x, \eta, \xi)+\mu G_{\eta}(x, \eta, \xi), \; \; x \in \Omega, \\ -M_{2}\left(\int_{\mathbb{R}^{N}\times\mathbb{R}^{N}}\frac{|\xi(x)-\xi(y)|^{^{p(x, y)}}}{p(x, y)|x-y|^{N+p(x, y)s(x, y)}} \ \ \ \ \ dxdy +\int_{\Omega}\frac{|\xi|^{\overline{p}(x)}}{\overline{p}(x)}dx\right) \left(\Delta_{p(\cdot)}^{s(\cdot)}\xi-|\xi|^{\overline{p}(x)}\xi\right)\\ \; \; \; = \lambda F_{\xi}(x, \eta, \xi)+\mu G_{\xi}(x, \eta, \xi), \; \; x \in \Omega, \\ \; \eta = \xi = 0, \; \; x \in \mathbb{R}^{N}\backslash \Omega, \end{array} \right. \end{equation*} $ where $ M_{1}(t), M_{2}(t) $ are the models of Kirchhoff coefficient, $ \Omega $ is a bounded smooth domain in $ \mathbb R^{N} $, $ (-\Delta)_{p(\cdot)}^{s(\cdot)} $ is a fractional Laplace operator, $ \lambda, \mu $ are two real parameters, $ F, G $ are continuous differentiable functions, whose partial derivatives are $ F_{\eta}, F_{\xi}, G_{\eta}, G_{\xi} $. With the help of direct variational methods, we study the existence of solutions for nonlocal fractional $ p(\cdot) $-Kirchhoff systems with variable-order, and obtain at least two and three weak solutions based on Bonanno's and Ricceri's critical points theorem. The outstanding feature is the case that the Palais-Smale condition is not requested. The major difficulties and innovations are nonlocal Kirchhoff functions with the presence of the Laplace operator involving two variable parameters.

Microglia, the resident immune cells in the central nervous system, can monitor the microenvironment and actively respond to ischemic stroke and other brain injuries. In this procedure, microglia and neurons can cross-talk via transmembrane chemokine, Fractalkine (CX3CL1), to impact one another. We used a rat model of multifocal microinfarcts induced by the injection of fluorescent microspheres into the right common carotid artery and examined the morphological alteration of blood vessels, microglia, astrocytes, and neurons at 6 h, 1, 7, and 14 days after modeling, along with neurobehavioral tests and the staining of CX3CL1 in this study. Our results demonstrated that in the infarcted regions, astrocytes and microglia activated in response to neuronal degeneration and upregulation of cleaved caspase-3, which occurred concurrently with vascular alteration and higher expression of CX3CL1. We provided sequential histological data to shed light on the morphological changes after modeling, which would help in the identification of new targets and the choice of the ideal time window for therapeutic intervention in ischemic stroke.

BackgroundCervical nerve root cysts are rare and easily missed or misdiagnosed in clinical practice. Although conventional surgery is effective for cervical nerve root cysts, it is limited by the small surgical field of view and operating range, relatively difficult procedure, and incomplete cyst resection. Microscope-assisted magnification of the surgical field of vision reduces the difficulty and ensures complete cyst resection.Case presentationA 58-year-old male patient was diagnosed with a cervical nerve root sleeve cyst on the right C7 vertebra with neurological symptoms. Microscope-assisted surgery was used as treatment. The cyst was completely removed by the microscope-assisted surgery, with satisfactory patient recovery. The surgery did not produce complications, such as spinal cord neurovascular injury, and the patient's symptoms disappeared quickly after surgery. During the 2-year follow-up, there was no complication and no recurrence.ConclusionMicroscope-assisted surgery in treatment of the C7 nerve root cyst could achieve a complete resection.

Abstract Background Extracellular electron transfer (EET) is essential in improving the power generation performance of electrochemically active bacteria (EAB) in microbial fuel cells (MFCs). Currently, the EET mechanisms of dissimilatory metal-reducing (DMR) model bacteria Shewanella oneidensis and Geobacter sulfurreducens have been thoroughly studied. Klebsiella has also been proved to be an EAB capable of EET, but the EET mechanism has not been perfected. This study investigated the effects of biofilm transfer and electron mediators transfer on Klebsiella quasipneumoniae sp. 203 electricity generation performance in MFCs. Results Herein, we covered the anode of MFC with a layer of microfiltration membrane to block the effect of the biofilm mechanism, and then explore the EET of the electron mediator mechanism of K. quasipneumoniae sp. 203 and electricity generation performance. In the absence of short-range electron transfer, we found that K. quasipneumoniae sp. 203 can still produce a certain power generation performance, and coated-MFC reached 40.26 mW/m2 at a current density of 770.9 mA/m2, whereas the uncoated-MFC reached 90.69 mW/m2 at a current density of 1224.49 mA/m2. The difference in the electricity generation performance between coated-MFC and uncoated-MFC was probably due to the microfiltration membrane covered in anode, which inhibited the growth of EAB on the anode. Therefore, we speculated that K. quasipneumoniae sp. 203 can also perform EET through the biofilm mechanism. The protein content, the integrity of biofilm and the biofilm activity all proved that the difference in the electricity generation performance between coated-MFC and uncoated-MFC was due to the extremely little biomass of the anode biofilm. To further verify the effect of electron mediators on electricity generation performance of MFCs, 10 µM 2,6-DTBBQ, 2,6-DTBHQ and DHNA were added to coated-MFC and uncoated-MFC. Combining the time–voltage curve and CV curve, we found that 2,6-DTBBQ and 2,6-DTBHQ had high electrocatalytic activity toward the redox reaction of K. quasipneumoniae sp. 203-inoculated MFCs. It was also speculated that K. quasipneumoniae sp. 203 produced 2,6-DTBHQ and 2,6-DTBBQ. Conclusions To the best of our knowledge, the three modes of EET did not exist separately. K. quasipneumoniae sp.203 will adopt the corresponding electron transfer mode or multiple ways to realize EET according to the living environment to improve electricity generation performance.

Colloidal semiconductor nanocrystals (NCs) attract significant interest in recent years due to their narrow and tunable emission wavelength in the visible range, as well as high photoluminescence quantum yield (PLQY), which are highly desired in display technologies. The high-quality NCs have been recognized as vital luminescent materials in realizing next-generation display devices. With further development, NCs with near-unity PLQY have been successfully synthesized through engineering of the core/shell heterostructure. However, as the external quantum efficiency (EQE) of the nanocrystal light-emitting diodes (LEDs) approaches the theoretical limit of about 20%, the low out-coupling factor proposes a challenge of enhancing the performance of a device when using the spherical QDs. Hence, the anisotropic NCs like nanoplatelets (NPLs) are proposed as promising solutions to improve the performance of nanocrystal LEDs. In this review, we will summarize the synthetic strategies of two-dimensional (2D) NPLs at first. Then, we will introduce fundamental concepts of LEDs, the main approaches to realize LEDs based on nanoplatelets, and the recent progress. Finally, the challenges and opportunities of LEDs based on anisotropic NCs are also presented.

Rice dwarf virus (RDV) is transmitted by insect vectors Nephotettix virescens and Nephotettix cincticeps (Hemiptera: Cicadellidae) that threatens rice yield and results in substantial economic losses. RDV induces two volatiles ((E)-β-caryophyllene (EBC) and 2-heptanol) to emit from RDV-infected rice plants. However, the effects of the two volatiles on the olfactory behavior of both non-viruliferous and viruliferous N. virescens are unknown, and whether the two volatiles could facilitate the spread and dispersal of RDV remains elusive. Combining the methods of insect behavior, chemical ecology, and molecular biology, we found that EBC and 2-heptanol influenced the olfactory behavior of non-viruliferous and viruliferous N. virescens, independently. EBC attracted non-viruliferous N. virescens towards RDV-infected rice plants, promoting virus acquisition by non-viruliferous vectors. The effect was confirmed by using oscas1 mutant rice plants (repressed EBC synthesis), but EBC had no effects on viruliferous N. virescens. 2-heptanol did not attract or repel non-viruliferous N. virescens. However, spraying experiments showed that 2-heptanol repelled viruliferous N. virescens to prefer RDV-free rice plants, which would be conducive to the transmission of the virus. These novel results reveal that rice plant volatiles modify the behavior of N. virescens vectors to promote RDV acquisition and transmission. They will provide new insights into virus–vector–plant interactions, and promote the development of new prevention and control strategies for disease management.

ObjectiveThis study aimed to investigate the sensory and motor innervation of “Taichong” (LR3) and “Ququan” (LR8) in the rat and provide an insight into the neural relationship between the different acupoints in the same meridian.MethodsThe LR3 and LR8 were selected as the representative acupoints from the Liver Meridian and examined by using the techniques of regional anatomy and neural tract tracing in this study. For both acupoints, their local nerves were observed with regional anatomy, and their sensory and motor pathways were traced using neural tract tracing with single cholera toxin subunit B (CTB) and dual Alexa Fluor 594/488 conjugates with CTB (AF594/488-CTB).ResultsUsing the regional anatomy, the branches of the deep peroneal nerve and saphenous nerve were separately found under the LR3 and LR8. Using single CTB, the sensory neurons, transganglionic axon terminals, and motor neurons associated with both LR3 and LR8 were demonstrated on the dorsal root ganglia (DRG), spinal dorsal horn, Clarke’s nucleus, gracile nucleus, and spinal ventral horn corresponding to their own spinal segments and target regions, respectively. Using dual AF594/488-CTB tracing, it was shown that the sensory and motor neurons associated with LR3 were separated from that of LR8.ConclusionThis study demonstrates that LR3 and LR8 are innervated by different peripheral nerves, which originated from or terminated in their corresponding spinal segments and target regions independently through the sensory and motor pathways. These results provide an example for understanding the differential innervation between the different acupoints in the same meridian.

Porcine circovirus 3 (PCV3) is an emerging virus, causing substantial economic losses in pig populations, that was first detected in 2016. Furthermore, the virus has already been reported in Europe, the Americas, and Asia, including China, indicating that the virus has spread worldwide. However, the molecular epidemiology of PCV3 still needs further study. To investigate PCV3 epidemiological characteristics in China, 2707 serum samples of pigs were randomly collected from 17 provinces in China between September 2018 and March 2022 and analyzed via PCR assays. The study showed that PCV3 infection was prevalent in the overall population with 31.07% (841/2707) and 100.0% (17/17) at sample and province levels, respectively, though the positivity rate of PCV3 varied from 7.41 to 70.0% in different provinces, suggesting that PCV3 infection has a widespread distribution in China. We selected 22 serum samples from different regions that had high levels of viral DNA for amplification and sequenced their ORF2 (Cap) gene. According to the phylogenetic analysis, all isolates in the current study could be grouped into two separate subclades, with 15 strains belonging to clade 3a and 7 strains belonging to clade 3b, indicating that PCV3a and PCV3b were the predominant subtypes in the regions of China studied. Meanwhile, additional analysis revealed that the capsid gene sequences identified in this study displayed 97.46~99.8% nucleotide (nt) and 97.06~100% amino acid (aa) sequence similarity with other PCV3 available reference strains, respectively. In general, our studies provide important insights for understanding the prevalence and evolution of PCV3 in China and will guide future efforts to develop measures for preventing and controlling the disease.

BackgroundMelatonin has been shown to play a protective role in the development and progression of cancer. However, the relationship between alterations in the melatonergic microenvironment and cancer development has remained unclear.MethodsWe performed a comprehensive investigation on 12 melatonergic genes and their relevance to cancer occurrence, progression and survival by integrating multi-omics data from microarray analysis and RNA sequencing across 11 cancer types. Specifically, the 12 melatonergic genes that we investigated, which reflect the melatonergic microenvironment, included three membrane receptor genes, three nuclear receptor genes, two intracellular receptor genes, one synthetic gene, and three metabolic genes.ResultsWidely coherent underexpression of nuclear receptor genes, intracellular receptor genes, and metabolic genes was observed in cancerous samples from multiple cancer types compared to that in normal samples. Furthermore, genomic and/or epigenetic alterations partially contributed to these abnormal expression patterns in cancerous samples. Moreover, the majority of melatonergic genes had significant prognostic effects in predicting overall survival. Nevertheless, few corresponding alterations in expression were observed during cancer progression, and alterations in expression patterns varied greatly across cancer types. However, the association of melatonergic genes with one specific cancer type, hepatocellular carcinoma, identified RORA as a tumor suppressor and a prognostic marker for patients with hepatocellular carcinoma.ConclusionsOverall, our study revealed decreased melatonergic gene expression in various cancers, which may help to better elucidate the relationship between melatonin and cancer development. Taken together, our findings highlight the potential prognostic significance of melatonergic genes in various cancers.

In this paper, the variable-order fractional Laplacian equations with variable exponents and the Kirchhoff-type problem driven by p·-fractional Laplace with variable exponents were studied. By using variational method, the authors obtain the existence and uniqueness results.

This paper is devoted to derive optimality conditions and duality theorems for interval-valued optimization problems based on gH-symmetrically derivative. Further, the concepts of symmetric pseudo-convexity and symmetric quasi-convexity for interval-valued functions are proposed to extend above optimization conditions. Examples are also presented to illustrate corresponding results.

In this paper, we present the gH-symmetrical derivative of interval-valued functions and its properties. In application, we apply this new derivative to investigate the Karush−Kuhn−Tucker (KKT) conditions of interval-valued optimization problems. Meanwhile, some examples are worked out to illuminate the obtained results.

P1 protein, the most divergent protein of virus members in the genus Potyvirus of the family Potyviridae, is required for robust infection and host adaptation. However, how P1 affects viral proliferation is still largely elusive. In this work, a total number of eight potential P1-interacting Arabidopsis proteins were identified by the yeast-two-hybrid screening using the turnip mosaic virus (TuMV)-encoded P1 protein as the bait. Among which, the stress upregulated NODULIN 19 (NOD19) was selected for further characterization. The bimolecular fluorescent complementation assay confirmed the interaction between TuMV P1 and NOD19. Expression profile, structure, and subcellular localization analyses showed that NOD19 is a membrane-associated protein expressed mainly in plant aerial parts. Viral infectivity assay showed that the infection of turnip mosaic virus and soybean mosaic virus was attenuated in the null mutant of Arabidopsis NOD19 and NOD19-knockdown soybean seedlings, respectively. Together, these data indicate that NOD19 is a P1-interacting host factor required for robust infection. [ABSTRACT FROM AUTHOR]